[HN Gopher] Moderna's HIV vaccine has officially begun human trials
___________________________________________________________________
Moderna's HIV vaccine has officially begun human trials
Author : grawprog
Score : 641 points
Date : 2022-01-31 17:16 UTC (5 hours ago)
(HTM) web link (www.them.us)
(TXT) w3m dump (www.them.us)
| somesanityplz wrote:
| hnarn wrote:
| I have no idea what you're trying to say.
| khazhoux wrote:
| Sadly, given that it's a new (throwaway?) account used to
| post in a thread about a vaccine, there's a high chance this
| is another neo-anti-vaxxer, here to tell us why this is "not
| a vaccine" and all that.
| somesanityplz wrote:
| I am just making a couple of considerations about you,
| audience, considering I silently read what you comment for
| years already. This is not a throwaway account. I just felt
| the need to express my opinion, if you are sad about that,
| and the only way to answer me is to label me as a "neo-
| anti-vaxer" you are just demonstrating my point.
| khazhoux wrote:
| But see, you didn't actually make a point in your
| original comment. I don't mean that rudely. You referred
| to the "arrogance [we] likely use to discuss the
| correctness of [our] code." What are actually saying
| here?
|
| If you want to engage in discussion, I encourage you to
| use plain language. Accuse the community directly of
| whatever charge you're bringing, and then we can debate.
| somesanityplz wrote:
| Would you deploy in production a software (which lack of
| safety could be critical) without being sure (or have
| proof) if it will effectively work as expected in 1+
| years?
|
| Would you be relaxed being the administrator of such a
| software?
| [deleted]
| khazhoux wrote:
| All the manners in which the vaccine could have been
| tested, were employed before deployment. The only thing
| that wasn't done, as you note, is to wait for XX number
| of years to see long-term side effects. So in fact, we
| don't know what the effects of this vaccine will be in 10
| years -- because the only way to know that is to wait 10
| years. But... there is also no indication, from similar
| vaccines, that "something terrible" happens in 10 years.
|
| A lot of people out there are just imagining, out of
| nowhere, than in 10 or 20 years, everyone who got the
| vaccine is gonna get autism or sprout a third nipple or
| keel over dead. But they're just imagining this. I can
| imagine a lot of things too... like, who here can prove
| to me that the new Doritos flavor introduced last year
| won't trigger brain cancer in 20 years? Anyone??
| [deleted]
| temptemptemp111 wrote:
| hn_throwaway_99 wrote:
| As I understand it, the reason an HIV vaccine has been so
| difficult to create is that HIV mutates so easily. I understand
| the basics behind how mRNA vaccines are generated, but I don't
| understand why this approach would be expected to have any more
| success in evading the high mutation potential of HIV than other
| vaccine types. After all, it was even a concern with new
| coronavirus variants that the original Moderna vaccine would be
| less effective against them (and, indeed, while the original
| vaccine _is_ still highly effective against all variants, my
| understanding is that it is less so than the original variant).
| And SARS-COV-2 mutates much less easily than HIV.
|
| Can someone with more knowledge explain the thought process
| behind this?
| throw895389 wrote:
| oblio wrote:
| > Here's my take. This is the long term "mRNA platform"
| product plan slowly coming to fruition.
|
| Cool! When am I getting my free 5G?
| ismail wrote:
| Your comment insinuates a conspiracy theory, equating OP
| comment with theories of 5g causing COVID. It does not add
| much to the discussion and comes across as dismissive.
|
| My experience is that as soon as we make a judgement call
| about someone, and put them in a pre-conceived box that we
| do agree with, we are unable to learn.
|
| I went and re-read OP post. nothing in it is close to what
| you are insinuating.
|
| Yes there may be some unsubstantiated claims, or calling
| out faucci but shutting down discussions with comments like
| yours are unhelpful.
| oblio wrote:
| The video they linked contains a cherry picked selection
| of quotes from Faucci and presumably pharma execs about
| accelerating vaccine approvals and arguing that a
| pandemic would help with that.
|
| Considering the rest of the comment and the throwaway
| account, yeah, for sure the comment was in conspiracy-
| land.
|
| My comment was useless, yes. Flagging it was probably
| much more impactful.
| emiliobumachar wrote:
| I definitely don't have any knowledge on the topic. Here are my
| crackpot opinions:
|
| 1) Maybe many or most infected have a single strain each, and a
| targeted vaccine to each's strain could work as a treatment,
| similarly to the tetanus and rabies vaccines. Even if not a
| full cure, could be a way to halt the disease progression with
| lower cost and side effects than the current treatments
| available.
|
| 2) HIV spreads relatively slowly, so maybe flu-style annual
| vaccinations to at-risk groups for hot strains could be enough
| to actually revert the epidemic over decades.
| f6v wrote:
| Regarding your second point, isn't HIV a preventable disease?
| In the areas where the prevalence is in double digits, people
| don't seem to be using condoms or taking other precautions.
| Why would they be taking vaccine every year?
| arcticbull wrote:
| It's a lot easier to get folks to agree to one or two shots
| one time than to convince them to change their sexual
| practices, one would imagine.
| f6v wrote:
| I somewhat agree, but condoms aren't just for HIV and
| save from other potentially lethal diseases. So the
| benefit is just enormous, yet folks still don't use them.
| At the same time, look the vaccination rates in the
| Eastern Europe. I suspect it's somewhat hard to get
| people vaccinated against the disease they don't take
| seriously. I mean, HIV is horrible. Yet so many people
| ignore protection.
| Qem wrote:
| The vaccine wouldn't mess with sexual pleasure, something
| that hampers adoption of condoms. While condoms transmit
| pressure sensation just fine, the shearing sensation is
| diminished. Older men with mild ED may lose erection in the
| interval necessary to apply a condom. I believe there is
| space to disruptive innovation in the condom market.
| bobbyasdfasdf7 wrote:
| getting a shot once a year is way easier than a very
| expensive pill every day (prep) or even using a condom
| every time you have sex.
| thebradbain wrote:
| I'm not a doctor, but as a gay man: it's my understanding HIV
| doesn't mutate in the same way a disease like Covid does, at
| least not in the sense that there's as many opportunities to
| spread (i.e. not airborne), so while HIV may actually mutate
| more in theory, it gets less chances to spread, so less
| completely-different variants become widespread.
|
| Also, as part of "stopping the spread" PrEP has existed for
| years. It's still proven to be effective protection against
| contracting HIV even if directly exposed (though it's a pill
| that must be taken every day rather than a vaccine). There's
| also PEP that helps make you undetectable (untransmissable) if
| you do contract it (and as such, it's no longer what many
| people still mistakenly regard as a death sentence).
|
| I honestly don't know why everyone who is sexually active isn't
| on PrEP (the federal government even mandates it be free to
| those without insurance in most cases)-- it should be as common
| practice as wearing a condom and birth control, yet its
| existence isn't even known to many people (especially among
| straight people).
| baristavibes wrote:
| I agree in that no straight people (that i know) consider
| PrEP, although according to a quick search the HIV prevalence
| rate is twenty times lower in my country compared to the US.
|
| Obviously the human brain statistician goes out the window
| when comparing a lifelong illness with a few hours of
| discomfort, but would it be generally safe/worth it to put
| the entire population on PrEP during sexual activity? I heard
| that HIV patients have noticable side effects with their
| meds.
| hn_throwaway_99 wrote:
| As a person on PrEP, it is only recommended for people at
| higher risk of HIV. In the West, that does _not_ include
| sexually active straight people unless you have other
| confounding factors (e.g. IV drug use, partners who are at
| higher risk, etc.). Essentially all gay men (or, more
| accurately, "men who have sex with men") _are_ at higher
| risk, which is why it is recommended for them.
| Gigachad wrote:
| >a lifelong illness
|
| Another thing to consider is it isn't a life long illness
| anymore. It's a life long subscription to a drug which
| neutralizes the threat and lets you live an entirely normal
| life without any problems other than having to take the
| drug periodically forever.
|
| Certainly not ideal but its not like you suffer illness.
| rswskg wrote:
| 'should be as common practice as wearing a condom and birth
| control, yet its existence isn't even known to many people
| (especially among straight people).' - not sure if you've
| seen who HIV effects, but if it especially effected straight
| people in the west (straight people in africa know full well
| about it) they would know about it.
| wan23 wrote:
| Small correction: PrEP (pre-exposure prophylaxis) and PEP
| (post-exposure prophylaxis) are both protocols for using
| drugs to prevent infection. You generally take PrEP drugs
| every day if you think you're in danger of being exposed, or
| alternatively take PEP if you think you have been exposed to
| HIV without any kind of protection, sort of like a morning
| after pill (but every day for a whole month).
| Drdrdrq wrote:
| > ...sort of like a morning after pill (but every day for a
| whole month).
|
| Does this mean that there is a cure, but it only works if
| taken shortly after exposure (and for a whole month)?
| tragictrash wrote:
| Not a cure, as that implies recovery from a full
| infection. It's preventing your body from becoming fully
| infected.
| whizzter wrote:
| It's a post-exposure treatment, don't think that
| qualifies as a cure. Same thing with the rabies vaccine,
| it'll only save your life if given before any symptoms
| occur (and the disease has entrenched itself in the
| body).
| roywiggins wrote:
| Something I learned today: PrEP also works "on demand", so
| for some people it may not be necessary to take it every
| day.
|
| https://www.aidsmap.com/news/jul-2020/demand-prep-highly-
| eff...
| abletonlive wrote:
| >I honestly don't know why everyone who is sexually active
| isn't on PrEP
|
| Side effects. People generally don't like to take drugs to
| prevent things if the chances of acquiring the illness is
| minimal. For example, if we had an approved vaccine for
| Malaria, we wouldn't just give it to everybody in the USA,
| and even if we did, many would not take it.
| hcarvalhoalves wrote:
| If there's less spread of any given variant (because of
| vaccines), you indirectly decrease the chance of mutation no? A
| virus doesn't mutate outside a host.
| macilacilove wrote:
| > As I understand it, the reason an HIV vaccine has been so
| difficult to create is that HIV mutates so easily.
|
| Nope. There are exactly two species of HIV since at least the
| '80s. HIV-1 and HIV-2. HIV however can trick the immune system
| into creating non-neutralizing antibodies, that can't fully
| prevent the progression of the infection.
|
| If you run a large pharma company you probably already make a
| lot of money from long-term HIV/AIDS treatment. From the CEO's
| perspective developing a HIV vaccine may shrink the
| antiretroviral market if at-risk groups vaccinate themselves.
| Therefore you prioritize more lucrative projects.
|
| HIV vaccine makes sense if: 1. You can hope for a general
| mandate of your product, or: 2. You are a small pharma company
| looking to make a name for yourselves.
|
| Regarding the benefit of mRNA vaccines over non-mRNA vaccines
| for HIV, I don't know. I have yet to learn if there is
| significant medical benefit to mRNA other than reduced cost and
| TTM.
|
| AFAIK mRNA does not enable producing new types of proteins,
| only this time they are produced by your body, right?
| copo233 wrote:
| You're gonna need a citation or two for all of that.
| bluGill wrote:
| This conspiracy theory missed something important:
| competition. There are other companies with their own
| treatments either one the market or in development trying to
| take away your customers. If you can find a better treatment
| and roll it out you get all that money, if you don't you risk
| someone else finding it first and taking away all your sales
| anyway.
| macilacilove wrote:
| The more effective treatment will shrink the market,
| therefore market forces incentivize competitors to
| cooperate. It is the same reason that the OPEC exists. It
| is called game theory, not conspiracy theory.
| helloworld wrote:
| "Prof. William Schief explains how the novel #HIV #vaccine
| being tested in human clinical trials can trigger the right
| #Bcells of the immune system to achieve the much sought after
| broadly neutralizing #antibodies."
|
| https://twitter.com/scrippsresearch/status/13581208549709127...
| dmix wrote:
| Direct link to video:
| https://www.youtube.com/watch?v=BrmXpMmvHWw
|
| This explains the background on broadly neutralizing
| antibodies that the other commenter `mlyle` mentions. Worth
| the watch.
| spamizbad wrote:
| One reason is that mRNA vaccines can be developed much faster
| than traditional vaccines. So the idea is you have a better
| chance of "outrunning" a strain.
| mpalczewski wrote:
| We get a new flu vaccine every year, is this much different?
| driverdan wrote:
| Yes. It takes a long time to generate the flu vaccine. The
| strains need to be selected long before the season starts
| so it's a bit of guess work. That's why effectiveness
| varies from year to year. mRNA vaccines can be produced in
| high volumes much faster than traditional vaccines. It
| would allow the flu vaccine strains to be selected at a
| better time.
| xienze wrote:
| > One reason is that mRNA vaccines can be developed much
| faster than traditional vaccines. So the idea is you have a
| better chance of "outrunning" a strain.
|
| Is that why the response to Delta was "just take another dose
| of the original formulation" and the response to Omicron was
| "just take another dose of the original formulation until we
| have the new one made up in a few months"? And who doesn't
| see another strain taking over in the next few months,
| rendering this new formulation less effective than originally
| promised?
|
| My math may be off but there's been exactly one new Covid
| vaccine formulation in a little over a year, which is about
| how fast we crank out new flu vaccine formulations. Why
| exactly did we need to use mRNA tech to crank out new
| vaccines at the same speed as we did with traditional
| vaccines?
| SideburnsOfDoom wrote:
| > Why exactly did we need to use mRNA tech to crank out new
| vaccines at the same speed as we did with traditional
| vaccines?
|
| mRNA tech is a lot newer than "traditional vaccines". I do
| not expect that the mRNA process is run at the same speed
| with the same degree of confidence at the same number of
| facilities. Yet.
| asveikau wrote:
| I suspect the fact that we're in the middle of a pandemic
| has something to do with this, though.
|
| In particular, the demand is such that we urgently need
| hundreds of millions (or billions?) of doses. That takes _a
| lot_ of effort to roll out. Most vaccines probably don 't
| see use at that scale and speed. An HIV vaccine, for
| example, would probably initially only go out to
| communities with higher risk.
| f6v wrote:
| I think slowly will come the realization that mRNA vaccines
| aren't as fast to develop as people thought.
| Sputnik/AstraZeneca vaccines were released almost at the same
| time as Moderna/Pfizer. Yes, the latter were first commercial
| mRNA vaccines, but the technology is nevertheless rather
| mature. I watched a lecture by the people credited with
| creating mRNA vaccines and it turns out people have been
| working on the technology for decades.
|
| Now, the thing is that you can't just sequence a virus, do
| bioinformatics, synthesize mRNA and package it into a nano
| particle. I mean, you can, but chances are it's going to fail
| like the CureVac vaccine. The mRNA that gets packaged needs
| to be modified (I believe with alternative bases) to achieve
| desired effect.
|
| If mRNA vaccine was as magical as it was marketed, we
| wouldn't be getting 3-4(and soon 5?) doses of the same
| vaccine with the emergence of new variants. Rather, there
| would be delta- and omicron-specific vaccine.
| tiahura wrote:
| _I think slowly will come the realization that mRNA
| vaccines aren't as fast to develop as people thought._
|
| It took 2 days to develop the vaccine.
| https://nymag.com/intelligencer/amp/2020/12/moderna-
| covid-19...
| outworlder wrote:
| One single employee at Pfizer created 10 vaccine candidates
| in one day.
|
| > Now, the thing is that you can't just sequence a virus,
| do bioinformatics, synthesize mRNA and package it into a
| nano particle.
|
| You can, and that's exactly what was done. However, out of
| the 10 or so candidates, they selected a few of the more
| promising ones to continue research.
|
| They are fast to develop. However, there are other steps in
| the pipeline that aren't so fast.
|
| > The mRNA that gets packaged needs to be modified (I
| believe with alternative bases) to achieve desired effect.
|
| That's the easy part. The full mRNA sequence is not that
| large (https://berthub.eu/articles/posts/reverse-
| engineering-source...) and many of such substitutions can
| be done by algorithms. Now, maybe the modified protein
| won't fold right. That's not as easy (although, we can
| compute how it will fold now).
|
| > If mRNA vaccine was as magical as it was marketed, we
| wouldn't be getting 3-4(and soon 5?) doses of the same
| vaccine with the emergence of new variants.
|
| If we were reckless and just wanted to inject someone with
| the latest update, this could be done in a matter of days.
| Human trials took months and people still complained that
| it was 'developed too quickly'. Then there's logistics.
| f6v wrote:
| I think you underestimate the effort needed to create an
| immunogenic vaccine candidate that doesn't have unwanted
| side effects. That's one of the reasons CureVac failed:
| https://www.nature.com/articles/d41586-021-01661-0
|
| And yes, AlphaFold is a major milestone, but I don't
| think we've solved protein folding for good.
| glial wrote:
| > Rather, there would be delta- and omicron-specific
| vaccine.
|
| I think there are -- they just haven't made it through the
| trials and approval processes yet. These are press releases
| from Pfizer for whatever it's worth:
|
| Omicron: https://www.pfizer.com/news/press-release/press-
| release-deta...
|
| Mentions delta: https://cdn.pfizer.com/pfizercom/2021-07/De
| lta_Variant_Study...
| f6v wrote:
| Yes, but what I meant was those would be already
| approved.
| lhoff wrote:
| I assume that still has something to do with mRNA being a
| novel vaccine type. Therefore the regulatory bodies are
| still carefull. If Moderna, Biontech and other potential
| players show again and again that there process of
| developing new vaccines is safe, I'd guess the time to
| market will getting shorter and shorter.
| copperx wrote:
| What's the rationale behind your assertion?
| LeanderK wrote:
| you can't do this since you need studies and those take
| time. Depending in the size of your cohort and the
| current viral load in the population. Curevacs study had
| the problem that during this time in germany the corona-
| virus wasn't that common so nobody knew whether the
| vaccine is working.
|
| As I understood it, the actual vaccine was developed
| super quickly and then everybody waited for the results
| of the study.
| jsharpe wrote:
| Regulation will take time to catch up. We manage to
| create and approve a flu vaccine every year, and that's
| likely because the general process has been approved, and
| so each iteration is fast tracked. I don't think that's
| the case with mRNA vaccines yet.
| selectodude wrote:
| The omicron and delta vaccines have existed for awhile now.
| The FDA requires efficacy testing for each individual
| booster. If the omicron specific booster isn't better
| "enough" than a booster of the already approved vaccine,
| it's going to be suck in approval hell.
|
| Regulatory bodies need to adjust to the new speed of mRNA
| vaccine production if we want that sort of release
| schedule.
| vkou wrote:
| > If mRNA vaccine was as magical as it was marketed, we
| wouldn't be getting 3-4(and soon 5?) doses of the same
| vaccine with the emergence of new variants. Rather, there
| would be delta- and omicron-specific vaccine.
|
| Is this a problem with mRNA, a problem with the approval-
| for-vaccine-variants process, a problem with funding, or a
| problem with the politicians who thought COVID would
| magically go away by August 2021 (Never mind that most of
| the world was nowhere close to being vaccinated, and the
| millions of sick people throughout it were happily
| producing variants)?
|
| I am ignorant on most of these subjects, but I would be
| surprised if the mRNA part of that was the problem!
| f6v wrote:
| What I'm trying to say is that mRNA vaccines might not be
| faster to deliver to market because you still need to go
| though testing and approval.
| ceejayoz wrote:
| The annual flu shot indicates there is presumably a "same
| vaccine, slightly different strain" streamlined procedure
| that can be used. I'd expect the same to occur with COVID
| boosters over time.
| im3w1l wrote:
| The slow part is the safety testing right? If we had a
| robust enough theory of vaccines safety we could reduce
| that. How are the yearly flu shots tested anyway? Now, I
| would not take such a HIV shot. But for high risk groups,
| think promiscious homosexuals, it may eventually be worth
| it.
| f6v wrote:
| If we had robust enough theory of vaccine testing it
| wouldn't matter what kind of vaccine you develop, right?
| im3w1l wrote:
| Maybe, maybe not? Mrna vaccines are very customizable so
| they could be specifically engineered to avoid known
| safety issues for example.
| SideburnsOfDoom wrote:
| > it turns out people have been working on the (mRNA
| vaccines) technology for decades.
|
| if you mean "Developing mRNA vaccines from nothing to a
| working product" then yes, that's taken decades.
|
| I don't really think that fact has much to say about if
| when you're already making millions of doses of commercial
| mRNA vaccines around the world this year, how fast next
| year's version can be made, tested, approved, manufactured
| at scale and deployed. The challenges involved seem to non-
| overlapping.
|
| "delta- and omicron-specific vaccines" are coming soon, but
| this is still the very early days on mRNA vaccines, as a
| commercial mass-scale product.
| onlyrealcuzzo wrote:
| > Sputnik/AstraZeneca vaccines were released almost at the
| same time as Moderna/Pfizer
|
| Most of the time and cost is associated with the trials -
| not the actual development AFAIK.
|
| What would be more promising is if MRNA proves to be much
| more likely to pass trials. I think we need a lot more
| attempts at different viruses to have an idea here.
|
| Certainly - if this HIV vaccine /does/ work - that's a huge
| win for MRNA.
|
| > If mRNA vaccine was as magical as it was marketed, we
| wouldn't be getting 3-4(and soon 5?) doses of the same
| vaccine with the emergence of new variants. Rather, there
| would be delta- and omicron-specific vaccine.
|
| This is nonsense. The traditional vaccines don't work any
| better. They're worse. This is evidence MRNA is better than
| traditional vaccines.
| f6v wrote:
| > The traditional vaccines don't work any better.
|
| Didn't say they were. Rather that mRNA don't seem to be
| approved faster for the new variants.
|
| > This is evidence MRNA is better than traditional
| vaccines.
|
| Haven't been following the field that closely. I only
| seen one pre-print(probably Hungary?) where Sputnik was
| on par. Would love to see data if you're willing to
| share.
|
| Edit: I admit I'm a bit confused since I mixed
| "traditional vaccines" and Sputnik/AZ together. The
| latter aren't traditional since adenovirus-based vaccines
| haven't been previously deployed, same as mRNA vaccines.
| lobocinza wrote:
| The way I understand is that that design and manufacturing
| is the smaller share of the lead time for mRNA and non-
| mRNA. The pre-clinic and clinic trials along with any
| regulatory delay take most of the time. Still mRNA vaccines
| are better and cheaper than conventional vaccines after
| CAPEX is done. Both Moderna and Pfizer have trials running
| for Omicron.
| tialaramex wrote:
| Both the Oxford-AstraZeneca vaccine and Sputnik are using a
| pretty similar trick that gives them the speed-up. They
| still get to pick an arbitrary sequence, but they're
| smuggling it inside a virus instead of as mRNA.
|
| That's why the codename for the AstraZeneca vaccine is
| ChAdOx1, it's a Chimp Adenovirus as host for the sequence.
| Take this mild uninteresting chimpanzee virus, but tweak it
| to tell human cells to produce your arbitrary sequence
| instead of itself. The humans become immune to whatever
| your sequence was (and maybe to Chimp Adenoviruses?).
|
| I'm sure there are reasons this might be better in some
| cases, and it involved less bleeding edge technology which
| made it a safer bet in a pandemic, but the mRNA approach
| seems obviously more general and even perhaps more re-
| usable.
| semerda wrote:
| I wouldn't call it arbitrary sequence, it's a specific
| sequence ie. s protein for covid.
|
| Saying that, it's now a known cause of blood clotting in
| some recipients:
| https://www.science.org/doi/10.1126/sciadv.abl8213
|
| "chimpanzee adenovirus Y25 (ChAdOx1), human adenovirus
| type 5 (HAd-V-C5) and human adenovirus type 26 (HAdV-D26)
| -- the scientists found that ChAdOx1 had a strong
| negative charge, which meant that it attracted PF4, which
| has a positive charge."
| dpark wrote:
| > _and maybe to Chimp Adenoviruses_
|
| Which is a major problem with this technique. One of the
| other vaccines (J&J?) used a relatively harmless human
| virus and as I recall, some people with previous exposure
| had no effect from the vaccine.
| morpheuskafka wrote:
| Likewise, it would seem that after one vaccine using a
| given vector, completely unrelated vaccines using the
| same vector would be ineffective? So presumably they
| would eventually run out of all the accessible vectors.
| Vrondi wrote:
| So, we're in for a future of continuously taking vaccines
| that are in "beta test" status, for which no long term has
| elapsed, so knowing actual real-world long-term effects is
| not possible, but merely speculation. Lovely.
| tylerhou wrote:
| Knowing long-term effects (1+ years) is not a precondition
| of approval for most vaccines. It just so happens that
| vaccines usually take a long time for approval, so we end
| up knowing long-term effects as a side effect.
|
| This is because there generally isn't a known mechanism for
| vaccines to have long term effects. Not ruling out the
| possibility, but we understand how vaccines work pretty
| well. Also, most vaccines are subject to a cost/benefit
| analysis anyway (we don't give the rabies vaccine out to
| everyone) so the miniscule chance of having long term
| effects has to be weighed against the much more likely long
| term effects of the disease.
| ifyoubuildit wrote:
| > This is because there generally isn't a known mechanism
| for vaccines to have long term effects.
|
| I know a lot of people believe this, but as a developer
| who regularly deploys code to production, this mindset
| blows me away.
|
| I'm not saying that being a developer means I know
| anything about this. I'm well aware of my (our? I don't
| know what you do) peoples habit of thinking being good at
| our craft means we're also somehow suddenly good at
| others.
|
| But if I told someone that I don't need to know the
| effects of v7.1.3 before patching it because I can't
| think of a mechanism for it going wrong, and besides, we
| already released all those other versions and they were
| fine, I'd hopefully be fired.
|
| I get it, software and medicine are different things, and
| some things just aren't practical in meat space, but the
| mindset around testing is something that I think will
| always be difficult for me to understand after being in
| this occupation for so long.
| outworlder wrote:
| > But if I told someone that I don't need to know the
| effects of v7.1.3 before patching it because I can't
| think of a mechanism for it going wrong, and besides, we
| already released all those other versions and they were
| fine, I'd hopefully be fired.
|
| You are missing the point. If someone told you they are
| worried that your code is going to turn the CPU into
| strawberry jelly, you would be correct if you said
| 'there's no known mechanism that will cause that'.
| ifyoubuildit wrote:
| Analogies are always flawed, but in this one, the
| pharmaceutical is the code and the human population is
| the set of machines its going to run on. The adverse
| effect would be an error that happens during runtime.
|
| It's not quite strawberry jelly, but depending on the
| target you're writing for, you could destroy the actual
| hardware (think embedded devices).
|
| If you presuppose that adverse effects can't happen, then
| sure, your quip makes sense. But pharmaceuticals having
| adverse effects isn't some unimaginable thing, it's
| expected and tested for.
| snowwrestler wrote:
| The thing to understand about vaccines is that they
| trigger things that your body does all the time by
| itself. A vaccine is more like kicking off a job than
| deploying new source code.
| johnny22 wrote:
| I kinda think of it as if you were writing an unofficial
| third party client for a black box remote API that
| doesn't want third party clients and can update all their
| official clients in days or weeks in different ways.
| joshuamorton wrote:
| > But if I told someone that I don't need to know the
| effects of v7.1.3 before patching it because I can't
| think of a mechanism for it going wrong, and besides, we
| already released all those other versions and they were
| fine, I'd hopefully be fired.
|
| But this isn't what they're saying. They're saying that
| there are few to no ways for it to not have any
| detectable issues for 6 months and then suddenly go wrong
| (which I'll note is also true for software!). Canarying
| and staged rollouts are a good idea in software, as they
| are in medicine. But much like you don't think its
| necessary to canary v7.1.3 for a year, just in case it
| has a bug that makes it shut down suddenly after 200
| days, its probably not necessary to wait a year to see if
| a vaccine causes sudden acute liver failure after 7
| months, because there just isn't a biological mechanism
| for it to do that (the vaccine is already out of your
| body by that point!).
|
| And to the extend that such issues are possible (leap
| days can do weird stuff), we can look specifically for
| those mechanisms (like say monitoring for stuff that
| would lead to liver damage in the weeks after
| vaccination).
| ifyoubuildit wrote:
| > But this isn't what they're saying. They're saying that
| there are few to no ways for it to not have any
| detectable issues for 6 months and then suddenly go wrong
| (which I'll note is also true for software!).
|
| Over the years I've become a little obsessed with
| imagining the ways things can fail (I'm just as fun at
| parties as you can probably imagine).
|
| An example that immediately jumps to mind where that is
| not true for software would be something that quietly
| uses some resource that you didn't expect (open ports,
| filehandles, space on disk/memory, the space inside of
| however many bits you have for a field, anything like
| that). These are things that you don't know to test until
| you've seen them fail, and only then can you start to
| automate.
|
| One possible analogy here is cancer or autoimmune issues.
| If you get diagnosed with either of those today, they
| almost certainly started a while ago, they just weren't
| detectable until today. Or maybe they would have been if
| you knew exactly where to look, just like if you knew to
| keep an eye on how many ports you had left on your live
| server. (Not claiming these vaccines cause these things,
| I'm sure some peoples blood pressure started rising as
| they read this).
|
| The complexity of software is nowhere near that of the
| human body or populations of humans, and yet it can be
| incredibly hard to predict. Multiple backwards compatible
| versions on the client and server side, running on
| different hardware with different operating systems, all
| of these things changing over time. Unexpected behaviors
| can absolutely show up at any time.
|
| Of course you can't test it all, but you do what you can,
| and then after that you monitor very carefully, but its
| way more expensive to fix the problem after it reaches
| prod. In humans, there's a chance that its not just
| expensive, it's impossible.
| tylerhou wrote:
| Let's suppose that your software currently has an
| incident where the service is degraded. For every day you
| don't push a fix, you lose 0.X% of revenue.
|
| Some engineer creates a fix by turning off some recently
| added experiment responsible for the service degradation.
| The rollback passes all unit tests and integration tests.
| You know this fix is low-risk (maybe because your service
| was healthy for the ~1 year prior to the rollout). Even
| if there is some risk that this rollback breaks the
| service at some point in the future, in comparison to the
| known revenue loss the expected loss of that breakage
| would be minimal.
|
| Another engineer objects to the rollback saying that
| "they don't know of the long term effects of such a
| rollback." You try to counter their claims by showing
| that previous rollbacks were almost always successful,
| and when they caused another failure that failure was not
| nearly as bad as the original service degradation. Also,
| the rollback passes all tests. That engineer then repeats
| "we don't know of the long term effects of this
| particular rollback, and I'm skeptical that the fix is
| good because the failing experiment and rollback was
| identified so quickly."
|
| (Rollback vs. fix-forward doesn't actually matter; the
| point is that all available knowledge shows that the fix
| is low risk, historically supported, and that there is
| likely no mechanism for random failure in 6+ months.)
|
| Do you think it would be correct to prefer the second
| engineer's claims?
| copperx wrote:
| I'm pretty sure understanding the biology behind it all
| can help make predictions about the outcome in the same
| way that you know that merging a pull request isn't going
| to bring the entire internet down. I mean, it could. But
| there's no known mechanism that will trigger such an
| event.
|
| That reminds me of the first atomic bomb test. We weren't
| 100% sure that the atmosphere wasn't going to ignite with
| an atomic bomb, but those that knew the physics knew it
| was almost impossible.
|
| > "If, after calculation, [Compton] said, it were proved
| that the chances were more than approximately three in
| one million that the earth would be vaporized by the
| atomic explosion, he would not proceed with the project.
| Calculation proved the figures slightly less -- and the
| project continued."
|
| https://www.insidescience.org/manhattan-project-
| legacy/atmos...
| ifyoubuildit wrote:
| > I'm pretty sure understanding the biology behind it all
| can help make predictions about the outcome ...
|
| Of course it can, that's what you use to write your test
| plan. But I never (ever) rely on those predictions alone.
| Everyone who has done this long enough knows that if you
| don't test your code well enough before you push it out,
| it _will_ fail. Hell, it 'll even fail sometimes when you
| did thoroughly test it.
| copo233 wrote:
| Yeah but you know, as much as you know anything else
| really, that your code won't break your toaster.
| ifyoubuildit wrote:
| https://www.amazon.com/Tovala-Gen-Multi-Mode-
| Programmable-St...
| pixl97 wrote:
| Well, in computers our test plans generally run in
| seconds.
|
| If you had to push code and wait a year for feedback then
| how you tested and pushed code would change dramatically.
|
| Now imagine the environment you were pushing code to was
|
| 1. Always changing in very small ways that could
| sometimes have huge affects due to completely random
| variable changes you had no control over. 2. Every host
| your ran your software on 'could be' different in ways
| that are incompatible and you have no way of testing all
| of them.
|
| Welcome to the problem space of biology.
| ifyoubuildit wrote:
| Well said. But some people take this as "well we can't
| realistically do the exhaustive test, and we really want
| this thing, so let's assume the outcome will be
| positive". That's fine when it's your own choice, but
| it's not when you're forcing it on other people.
| AussieWog93 wrote:
| This is such an out of touch comment.
|
| I ask that you please speak to some people in South Africa
| or Botswana where almost 20% of the population live with
| HIV, including children (both victims of rape - there was
| and still is the belief that having sex with a virgin can
| cure AIDS - and children of HIV-positive mothers who were
| born with the condition).
|
| It's beyond inhuman, and if such a vaccine were to work it
| would be as impactful as the eradication of Polio (yes, I
| know it still exists in some places) or Smallpox.
| glitchc wrote:
| Seems to be an okay strategy for software...
| ausudhz wrote:
| So you think for other vaccine you know the "long term
| effects"
|
| What you define as "long term"? Because in my definition,
| in the "long term" we're all dead.
|
| The "long term" effects of many pathologies is also death
| for example.
| ceejayoz wrote:
| > Because in my definition, in the "long term" we're all
| dead.
|
| My wife's studio got a "everyone who takes the vaccine
| will die!" pamphlet pushed under the door, which gave us
| a good chuckle.
| mlyle wrote:
| Three things:
|
| - This isn't really the reason why mRNA is attractive here
| (see my other comment above). (Though, ability to
| iterate/try many protein combinations quickly in animal
| models was helpful).
|
| - Almost no drugs or treatments do we _really_ know the
| long term picture of. Running studies in a way that lets
| you detect effects far later in life isn 't practical.
|
| - When we're talking about treatments to prevent severe
| disease, bounding the consequences to be very, very likely
| to be well below the consequences of the virus times the
| likely infection chance is "good enough".
| ausudhz wrote:
| Not to mention the long term effects of COVID are known
| and way worst that what a vaccine can give you.
|
| Vaccine are building an immune response, they're not
| drugs that try to cope the symptoms (eg. Panadol) and
| they are the safest drugs out there.
|
| Is so interesting how people eat Panadol and many other
| drugs like candies (without reading the KNOWN side
| effects - which are also nasty), while they focus so much
| on things they know nothing about thinking that has
| mysterious "long term effects"
| epgui wrote:
| Exactly this. I would rather take the "most unsafe"
| vaccine of the last 30 years than take an Advil. (I am a
| biochemist)
| arcticbull wrote:
| The one that really surprises me that people take like
| candy is Tylenol/Panadol/Paracetamol/Acetaminophen. It's
| the leading cause of acute liver failure in the US. Among
| common OTCs, its active dose is I believe the closest to
| its lethal dose. Just 2-3X the recommended daily upper
| limit can cause liver damage, and when taken around
| alcohol, the toxicity is dramatically higher.
|
| I strongly doubt that Acetaminophen would be approved as
| an OTC drug if proposed today.
| Firmwarrior wrote:
| I never really gave much thought to how dangerous this
| stuff was until a year or so ago, Eric Engstrom (one of
| the creators of DirectX and a personal hero of mine)
| accidentally overdosed and died from it:
|
| > He died at a hospital in Seattle. His wife, Cindy
| Engstrom, said he had injured one of his feet in October,
| accidentally took too much Tylenol for pain relief and
| suffered liver damage.
|
| https://news.ycombinator.com/item?id=25423712
| mpalczewski wrote:
| abletonlive wrote:
| Could you elaborate on why you wouldn't take advil?
| mlyle wrote:
| Not the poster. Advil is pretty safe, but sometimes has
| horrific effects (e.g. Stevens Johnson Syndrome,
| catastrophic stomach bleeding, etc.)
|
| Also, NSAIDs are shown to slow healing from injury in
| most cases.
|
| Ibuprofen is terrifically useful but also a little scary
| for something we use so routinely.
|
| e.g. some parents gave their 7 year old a motrin, and all
| her skin sloughed off her body and she had brain damage
| and lost 80% of her lung function.
|
| https://www.cbsnews.com/news/jury-awards-63m-to-samantha-
| rec....
| BitwiseFool wrote:
| Fascinating, can you tell me more about your aversion to
| Advil? I haven never encountered anyone warning about it
| until now and would like to know more.
| Jenk wrote:
| you'd rather the long term effects of HIV?
|
| What a bizzarely banal thing to post.
| vmception wrote:
| mRNA treatments likely will accelerate the trial process
| because their purview is so limited, compared to other
| molecule based treatments.
|
| So more likely you'll just get over a shorter release cycle
| and the longer one gets deprecated, relegated to certain
| style of treatment that mRNA based investment and research
| will run laps around anyway, further pushing people to
| evaluate and prioritize mRNA versions.
|
| You can try to hold out for an arbitrary threshold of "long
| term" for your own comfort level. Its accurate that the
| state wont be helping you.
|
| mRNA is like a file for a 3D printer, telling the body what
| to print for. Other styles of treatments were showing the
| body the payload. We will definitely learn how often we can
| get the body to do this, but I wouldn't call it an inferior
| beta status. Its just as good (or bad) as the longer
| process for different kinds of treatment. Same efficacy,
| which allows me personally to not focus on that.
| epgui wrote:
| You're vastly overestimating the potential harms caused by
| vaccines.
| arcticbull wrote:
| Generally the long pole in vaccine approval is showing that
| it works - not that it's safe. If there's only a handful of
| cases worldwide, say for Ebola, then you have to vaccinate
| a few thousand people and wait for a period where a
| statistically significant portion would have caught the
| disease and then didn't. This can be _years_. There 's only
| a few cases per year, you can't just give a bunch of people
| Ebola to see if the vaccine works. They're not waiting for
| 'long-term side effects' to show up, they know they don't
| exist.
|
| However, with HIV as with COVID, there's a pretty
| significant installed base around the country so showing
| that it works isn't really a challenge.
|
| Usually only a few thousand or tens of thousands of folks
| participate in basically any drug trial, btw. We very well
| understand the risk profile of mRNA vaccines at this point,
| having deployed billions of them and studied the technology
| for 40+ years. And having studied vaccines for upwards of
| 300 years.
| ampdepolymerase wrote:
| I haven't looked into the Moderna vaccine but in general there
| are many ways to get rid of a virus. Using the typical B cell +
| viral glycoprotein is the most obvious way as viral activity is
| hard to detect when replicating inside a cell but there are
| many stages in the viral replication process which can be
| inhibited. Inhibiting protease cleavage of the viral
| polyprotein or preventing polymerase formation are all possible
| solutions. They don't really count as vaccines though.
| cdtwigg wrote:
| I am not an expert, but there has been a lot of hope recently
| that because we have much better understanding of protein
| structure (e.g.
| https://cen.acs.org/pharmaceuticals/vaccines/tiny-tweak-
| behi...) and because mRNA allows us to tightly control the
| genetic sequence, there is hope we could target some part of
| the virus that _is_ well-conserved across variants. e.g.:
| https://pharmaceutical-journal.com/article/feature/preventin...
| mlyle wrote:
| There's some known HIV "bnAbs", or broadly neutralizing
| antibodies. The thing is, these are not the antibodies most
| humans develop in response to HIV.
|
| Previous HIV vaccine attempts have only done a fair job at
| eliciting these broadly neutralizing responses. e.g. SAV001, a
| "whole killed" HIV vaccine, only produces broadly neutralizing
| antibodies in about a third of recipients (and less broadly
| neutralizing response in a much bigger fraction).
|
| The mRNA approach, like some recombinant approaches, seeks to
| generate just portions of envelope protein to tailor the
| response to produce these bnAbs.
| maxerickson wrote:
| The IAVA press release discusses some of this:
|
| https://www.iavi.org/news-resources/press-
| releases/2022/iavi...
|
| Sounds like the mRNA platform is being tested as a delivery
| mechanism for immunological work that was done separately.
| XorNot wrote:
| Specifically it's advantageous because bnAB development
| requires 2 separate immune stimulii applied over months.
| Injecting protein bolus (traditional vaccines) then
| requires something like 6+ separate, different vaccines -
| so 6 synthetic paths, production lines etc.
|
| mRNA eliminates all of that. The 2 immune pathways can be
| combined into 1 vaccine, and the multiple vaccines can all
| be produced with the same synthetic pipeline and the same
| distribution and administration requirements.
|
| mRNA may make a huge difference here.
| f6v wrote:
| I'm not familiar with vaccine tech. Can't you grow the
| peptide of interest and package it in a traditional vaccine?
| mlyle wrote:
| > Can't you grow the peptide of interest and package it in
| a traditional vaccine?
|
| Traditional way to do this is recombinant approaches
| (mentioned). These are also in progress. mRNA is much
| quicker to iterate, though. They tried a few candidate
| sequences in sHIV to guide their human vaccine development.
|
| mRNA vaccines are kind of neat in the way that they create
| a few day long pulse of new virus-like particles showing
| up, to ensure the immune system gets really annoyed.
| siver_john wrote:
| Strictly speaking you can, and not knowing the exact
| reasons this approach is moved to human trials where others
| have not, I can only conjecture.
|
| However, the mRNA vaccine may be more stable in a way that
| makes it easier to make or store or for entrance into the
| body. Not to mention purification steps may be easier. You
| don't need to make this in some exotic cell line which
| creates a protein soup you have to purify. It may be easier
| on the body (less likely to develop a severe immune
| reaction), or it may be better at generating a sufficient
| immune reaction because a lot of mRNA development has gone
| into finding molecules that are readily taken up by the
| immune system regardless of cargo.
|
| These are a few reasons I can think I am sure I am missing
| some and there may be a stated answer out there that I have
| yet to search for.
| mlyle wrote:
| > this approach is moved to human trials where others
| have not, I can only conjecture.
|
| Actually, a whole lot of recombinant approaches have
| moved to human trials (along with viral vector
| approaches). They early ones showed no efficacy; the
| newer ones we just don't know (yet).
|
| The main benefit of mRNA is iteration: you can try a
| whole lot of different protein mixes and see what works
| best in an animal model. A secondary benefit is that the
| sustained churning out of proteins for a few days seems
| to generate a much broader antibody response, making
| getting some of those elusive bnAbs more likely.
|
| A big problem with killed HIV vaccines and purified
| fragments of HIV is that growing virus in human immune
| cells is extraordinarily costly, and you really wouldn't
| want to have some live HIV leak through your purification
| process. So this is why we're _mostly_ talking about
| other approaches to make proteins (viral vectors,
| recombinant DNA in bacteria and other cells, mRNA
| vaccines, etc)
| siver_john wrote:
| >Actually, a whole lot of recombinant approaches have
| moved to human trials (along with viral vector
| approaches).
|
| I should have been more clear here, I meant specifically
| trials of what I presume could have been attempted if the
| vaccine was expressed as protein instead of mRNA. But
| thanks for the clarification. And the mention of viral
| vectors which are an area I was less aware of till
| recently but it has been cool to see them in more places.
| mlyle wrote:
| > I should have been more clear here, I meant
| specifically trials of what I presume could have been
| attempted if the vaccine was expressed as protein instead
| of mRNA.
|
| Yes, and one vaccine approach is getting a bacterium or
| other virus to make a lot of a protein you're interested
| in, and then purifying the stuff you're interested in and
| forming it into a vaccine product. These are recombinant
| approaches. E.g. https://en.wikipedia.org/wiki/AIDSVAX is
| exactly what you describe: a viral protein vaccine
| developed using recombinant approaches from e.g. Chinese
| hamster ovary cells
| https://pubmed.ncbi.nlm.nih.gov/8142140/
|
| The first was a hepatitis B vaccine developed in the
| 1970s where yeast cells were modified to make hepatitis B
| proteins. Then the HPV vaccine used the same approach,
| choosing proteins that would spontaneously assemble into
| a virus-like particle that triggers a strong immune
| response.
|
| Complicated proteins have to come from a living thing, in
| practice. So if you're going to administer a viral
| protein, it has to come from purifying virus that you've
| grown or from a recombinant approach of some kind (and
| growing HIV is problematic for multiple reasons).
| dnautics wrote:
| > "these are not the antibodies most humans develop in
| response to HIV."
|
| In many cases. One case, for example was identified from a
| prostitute in sub-saharan africa who managed to be completely
| HIV-free. It turned out she had a mutation in her antibodies
| that caused the antibodies to latch onto things with four
| sites instead of just 2 (think X shaped instead of V shaped).
| andrewflnr wrote:
| That sounds fascinating. Got any links or search terms?
| dnautics wrote:
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4136306/
| hn_throwaway_99 wrote:
| Thank you! Just the kind of explanation I was looking for,
| most appreciated.
| aleks224 wrote:
| >An "elite controller" is a person living with HIV who is
| able to maintain undetectable viral loads for at least 12
| months despite not having started antiretroviral therapy
| (ART) . Elite controllers are rare: for every two hundred
| people living with HIV, approximately one may be an elite
| controller (0.5%).
|
| > It is not entirely understood why some patients are able to
| achieve undetectable viral loads without ART.
|
| https://www.aidsmap.com/about-hiv/faq/what-elite-controller
| dillondoyle wrote:
| And undetectable === untransmittable. Just in case people
| here didn't know.
| hdjjhhvvhga wrote:
| I didn't know this. Could you explain the reason?
| Nbox9 wrote:
| CDC backing up this claim. Having an undetectable viral
| load prevents transmission during sex --- but likely not
| during needle sharing. The answer to why seems to be an
| obvious "because there are less virus particles". I'm
| linking a couple of scientific studies following couples
| having condomless sex where one partner is HIV positive,
| on ART with low viral load. Among the about 2000 couples
| in these studies there were no transmissions.
|
| https://www.cdc.gov/hiv/basics/livingwithhiv/protecting-
| othe... https://www.nejm.org/doi/full/10.1056/NEJMoa16006
| 93#t=articl... https://pubmed.ncbi.nlm.nih.gov/27404185/
| jl6 wrote:
| It does sound suspiciously like wishful thinking though,
| doesn't it? You can't sample all parts and all fluids of
| someone's body all the time. Maybe trace undetectable
| levels of the virus can be transmitted, and of course
| they are going to look like a "no transmission" case if
| you lack the ability to detect that amount of virus. And
| that's either not a problem (if trace levels = no
| symptoms), or a ticking time bomb waiting to find a host
| with the conditions that would enable mass viral
| replication back up to detectable levels.
| vsef wrote:
| There is no such thing as a trace/undetectable
| transmission. These studies have been going on a long
| time now with large numbers of participants, replicated
| in multiple countries/different populations. The results
| are very strong and not based on measuring viral levels.
| lixtra wrote:
| > You can't sample all parts and all fluids of someone's
| body all the time. Maybe trace undetectable levels of the
| virus can be transmitted...
|
| You don't need to be a 100% sure. Once the risk becomes
| small enough you can spend your time worrying about other
| risks.
| jl6 wrote:
| Now that may be entirely the right posture, but the
| triple equals signs in the post upthread did rather imply
| certainty.
| hashimotonomora wrote:
| Risks like these are orthogonal and additive. There's no
| reason to discard any risk but to hedge them.
| chucksmash wrote:
| Presumably the viral load required for transmission is
| greater than the viral load required for detection.
| whimsicalism wrote:
| My guess is it is more of a probabilistic thing than a
| strict threshold.
| stjohnswarts wrote:
| That seems like a big if? maybe 0.5% of people actually
| are succeptable to the lowered viral load. Have studies
| been done that would detect such a population?
| mlyle wrote:
| One reason we believe this is that we can typically
| detect virus quantities way too small to reliably
| replicate in culture, and believe that in vivo infection
| is even harder than in culture (because of innate immune
| response and the body not being composed just of the most
| susceptible cells).
|
| You generally can't measure infectious dose directly
| without a highly unethical challenge study. You can
| sometimes know concentrations that did or didn't result
| in infection in various real world scenarios, and
| sometimes you have circumstantial evidence (e.g. you can
| know how much virus a person sheds, and what proportion
| of a room with certain ventilation quantities got
| infected).
| jxramos wrote:
| that's what I would think, it's got to be quantifiable:
| some sensitivity metric of the concentration of virus
| particles the device can detect vs the minimum quantity
| which is needed for infection. It's clear we can
| articulate these matters in the abstract, how does one go
| about actually measuring such a thing?
| matheusmoreira wrote:
| Viral load. Number of viral copies per volume of fluid.
|
| Merely exposing someone to a virus does not necessarily
| result in widespread infection. A low enough number of
| copies could be neutralized by the host's immune response
| before it has a chance to spread significantly. How low
| this number is depends on the virus. For example,
| COVID-19 load is higher in symptomatic patients.
|
| Chronic viral infections are managed by reducing as much
| as possible the number of viral copies in circulation.
| Risk of transmission is mitigated when number of copies
| is low enough. There are studies showing risk of HIV
| transmission approaches zero when HIV load < 200
| copies/ml. Ideal would be HIV load < 50 copies/ml or
| undetectable.
|
| https://en.wikipedia.org/wiki/Viral_load
|
| https://en.wikipedia.org/wiki/Minimal_infective_dose
|
| https://en.wikipedia.org/wiki/Management_of_HIV/AIDS
|
| https://en.wikipedia.org/wiki/Viral_load_monitoring_for_H
| IV
| hashimotonomora wrote:
| At that low virion count it's more about the probability
| that a virion will attach to the correct CD4 receptor and
| be able to work inside the cell. It's not about the
| host's immune system defeating or being defeated on a
| number basis.
| baq wrote:
| No detectable virus means no transmissible virus.
| Drdrdrq wrote:
| To reiterate the question, why is that?
| space_fountain wrote:
| I'm not a biologist and this is based on general
| knowledge and some quick google searches but:
|
| We're quite good at detecting viruses if we really want
| to. PCR can amplify DNA so much that we can detect even
| 50 viruses per milliliter of blood. A milliliter seems
| like actually a lot of blood to get into someone else and
| your innate immune system is capable of finding and
| neutralizing small amounts of contagions relatively well
| even if it's never seen it before. I do suspect this is a
| statistical impossibility though probably you could
| somehow get incredibly unlucky, for example in your blood
| momentarily all the free floating viruses end up in the
| same bit of blood and that somehow gets into someone
| else, but I think we can all realize that probability is
| tiny and in practice I don't think there are any examples
| of transmission with undetectable levels of HIV.
| XzAeRosho wrote:
| That's the million dollar question
| JulianMorrison wrote:
| Detection means there is enough virus physically present
| in the sample for the detection technology to identify
| it.
|
| Infection requires virus particles to be physically
| present in transmission vectors (fluids, droplets, etc).
| There's generally also a dose-response effect where more
| particles means more chance of evading the immune system
| well enough to establish replication in the victim.
|
| So a lack of anything to detect, means a lack of anything
| to spread an infection.
| Drdrdrq wrote:
| Thank you, makes sense!
| _Microft wrote:
| _> So a lack of anything to detect, means a lack of
| anything to spread an infection._
|
| One should add that for that the threshold for detection
| has to be lower than the threshold for infection.
|
| Example: let the detection threshold be 10 particles/ml
| and the infection threshold be 100 particles/ml (*) ->
| then undetectable implies that it is very improbable that
| an infection will take place.
|
| (*) This is a very crude description. Think of it like
| this: Every single virion (virus particle) has a very low
| probability of causing an infection itself but there is a
| high number of them and for one them it might just work
| out (higher viral load -> higher risk of successful
| infection)
| hashimotonomora wrote:
| False. Detectable is an experimental limitation of a
| given measurement system. Even one single virion can
| infect a host.
| balaji1 wrote:
| so everybody gets it soon?
| s1artibartfast wrote:
| Is this related to the concept of original antigenic sin?
| [deleted]
| erglkjklrh wrote:
| hackerlytest wrote:
| [deleted]
| sharken wrote:
| If a HIV vaccine really is happening, that will really brighten
| the memory of the last two COVID years.
|
| And as always there are some great insights to the inner working
| of the vaccine, Hacker News doesn't disappoint.
| csours wrote:
| A LOT of really good science was funded over the last two
| years. It will be a while before it's all understood and
| integrated. It does give me a little bit of hope.
| Pooge wrote:
| From my understanding, the effectiveness of the vaccine is
| measured by monitoring - in the real world - how many vaccinated
| people of a group catches the virus compared with how many
| unvaccinated did: how would it work in this case? I guess it
| would just take a lot of years to come up with a good
| approximation.
| TameAntelope wrote:
| https://www.hiv.gov/hiv-basics/overview/data-and-trends/stat...
|
| This info should give you a better idea of how one might
| compose a set of trial groups for something like this.
| Pooge wrote:
| Thank you, this is a good resource!
|
| But in order to have a good approximation of the
| effectiveness, we would need people to get infected. If I
| simplify, I would get vaccinated and stop using protection
| (i.e. condoms) during intercourse, but then I may catch it
| and end up living for life with HIV (contrast to COVID where
| you still have fairly reasonable chances to recover from).
| How would trials work for things like this?
|
| Please correct me if I'm wrong, but I hope you see where I'm
| going with this.
| TameAntelope wrote:
| Not sure what the issue is. Tens of thousands of people get
| HIV each year; all you need to do is give some of them the
| vaccine and see if those people get HIV as much as the
| people you didn't give the vaccine to.
|
| People are already getting infected, we don't need to do
| anything for that to continue to happen.
| Pooge wrote:
| Absolutely no issue. I was just wondering how we would
| possibly approach it. And got my answer! Thanks.
| s1artibartfast wrote:
| Easier said than done. In 2019, the estimated number of
| HIV infections in the U.S. was 34,800 and the rate was
| 12.6 per 100,000 people. Consider that normal clinical
| trials are a few hundred people. Men who have sex with
| men are ~25x more likely to get HIV, so you are still
| looking at 1 in 3,000 per year. You are talking about
| some pretty huge trials here even if you are focusing on
| MSM only.
| [deleted]
| kettleballroll wrote:
| This will be Phase 1 clinical trials, ie they're mostly about
| side effects (and potentially dosage): ie they'll mostly check
| whether this will kill you / which dosage van be considered
| mostly safe. But at later trial stages, this will be one method
| to do this. Another and mich simpler one: you check whether the
| vaccinated people develop the antibodies you're looking for.
| mikaeluman wrote:
| I remember growing up being terrified of HIV/AIDS. The idea of
| something being permanent and transmissible via sex, and
| literally dismounting your immune defense to all other diseases
| on the planet...
|
| To this day it still terrifies me, even though the treatments
| have become so good.
|
| Each year it seems there are new stories about HIV research, and
| progress keeps being made. I pray for positive results and am
| really amazed. We have a lot to be thankful for.
| suifbwish wrote:
| It would not surprise me if HIV was not 100% natural.
| db1234 wrote:
| Does anyone know if mRNA tech can be potentially used to cure
| food allergy in the future? I know that the pattern is to train
| immune system to recognize a foreign object and attack it but is
| it possible to train immune system using mRNA to not attack in
| certain cases? I did come across a paper from 2018 regarding
| potential use of mRNA to fight food allergy but I haven't come
| across any updates since then.
| ianlevesque wrote:
| I am very not a biologist but I can't picture how this would
| work. Immunotherapy for food allergies, specifically peanuts,
| involves basically microdosing the allergen until the immune
| system chills out. mRNA wouldn't help there, even if you made a
| vaccine that exposed a peanut protein it'd have the opposite
| effect you were going for. If you took a different approach and
| expressed a protein that suppresses the immune response, then
| in just days when the mRNA degrades the effect would be lost.
| I'm sure we will get many miracles from mRNA tech but this
| doesn't seem like a likely one to me.
| abeppu wrote:
| I'm a bit confused by the timing of this. Here's a press release
| from only a couple months ago, in which a Moderna partnership on
| an mRNA vaccine showed some benefit in macaques, but mostly in
| delaying infection (i.e. most macaques in the treatment group
| still got SHIV). Only two of seven in the treatment group
| actually remained uninfected. It sounded like researches wanted
| to refine and validate their protocol before moving to human
| trials.
|
| > "We are now refining our vaccine protocol to improve the
| quality and quantity of the VLPs produced. This may further
| increase vaccine efficacy and thus lower the number of prime and
| boost inoculations needed to produce a robust immune response. If
| confirmed safe and effective, we plan to conduct a Phase 1 trial
| of this vaccine platform in healthy adult volunteers," said Dr.
| Lusso.
|
| I interpreted "If confirmed safe and effective" to mean that more
| animal tests would happen.
|
| https://www.nih.gov/news-events/news-releases/experimental-m...
| meepmorp wrote:
| 2 out of 7 macaques didn't get infected after 13 weekly (anally
| administered) exposures to SHIV. The other 5 averaged 8
| exposures before infection took place vs 3 exposures in the
| control group.
|
| That's actually pretty good at preventing infection - 28.5%
| avoided infection completely, with the remainder clearly having
| a much more robust immunity than control.
| abeppu wrote:
| I mean, it seems like it did _something_ meaningful. But if
| you were part of an at-risk population, how promising would
| you really consider an animal trial that, for most treatment
| subjects, delayed infection by 5 weeks? Note, these animals
| had received multiple vaccines/boosters spaced out over a
| year before they were exposed to SHIV, i.e they spent 10x as
| long being vaccinated as they resisted infection.
| bluGill wrote:
| Better than nothing. Maybe not enough for me to stop
| whatever other practices I'm doing to reduce risk, but it
| seems like a good shield in case one of those others fail.
| abeppu wrote:
| But the alternative isn't nothing.
|
| E.g. one class of alternatives is PrEP which is very
| effective, well-tolerated in many patients, and depending
| on country, pretty affordable. Oh, maybe for various
| reasons, regularly getting and taking pills is difficult
| for some populations, and a series of injections makes
| more sense? Subdermal injections for PrEP are also in the
| works and look like they would work for more than a year.
|
| I would love there to be a really highly effective
| vaccine. But PrEP sets the bar relatively high for a
| vaccine to actually be an improvement, right?
|
| https://www.cdc.gov/hiv/risk/prep/index.html
| https://www.aidsmap.com/news/mar-2021/reformulated-
| islatravi...
| TaylorAlexander wrote:
| I'm curious how that compares to PrEP but I suppose both
| would be better than one.
| pandemicsoul wrote:
| "PrEP reduces the risk of getting HIV from sex by about 99%
| when taken as prescribed," according to the CDC:
| https://www.cdc.gov/hiv/basics/prep/prep-effectiveness.html
| f6v wrote:
| It's hot tech, maybe driven by the desire to pump share prices.
| Koffiepoeder wrote:
| Honest question: since making mrna candidate vaccines is
| apparently so easy, would it be feasible to include mrna of
| multiple disease proteins in one vaccine? Is there hope for e.g.
| a general std-vaccine that covers all of the most common std's?
| Veliladon wrote:
| Yes. On the respiratory side Moderna already have a vaccine in
| development for quadrivalent flu, COVID-19 and RSV in the same
| shot projected for a 2023 release.
| vecr25 wrote:
| Original press release:
| https://investors.modernatx.com/news/news-details/2022/IAVI-...
| NotChina wrote:
| 8f2ab37a-ed6c wrote:
| I wonder if we'll see HSV also addressed by this new wave of mRNA
| vaccines, or if it's just not top of mind for companies and
| researchers due to its "mostly benign" nature. At least until
| one's immune system starts to weaken with advanced age and it
| starts to cause all sorts of problems, but perhaps by then it
| gets swept under the "problems of aging" rug.
| Unklejoe wrote:
| Dr. Friedman and team at UPenn are working on exactly this. An
| mRNA based prophylactic (and also potentially therapeutic)
| vaccine for HSV. I think they were originally using some other
| form of vaccine (a protein vaccine?), but then realized that
| mRNA was a lot better. He has posted a few video updates on the
| progress, and it looks good, but of course it hasn't entered
| phase 1 yet (supposed to start this year).
| TaylorAlexander wrote:
| Yes there are multiple efforts with that one being I think
| the most promising. They hope to cure the first humans of HSV
| in 2024. I believe they have all the funding they need for
| now, having raised over $500k.
|
| More details on this subreddit and specifically this sticky:
| https://www.reddit.com/r/HerpesCureResearch/comments/kg66ds/.
| ..
| 8f2ab37a-ed6c wrote:
| It's interesting how small some of those grants and funding
| pools are compared to what you see in startup land.
|
| Maybe this is just the economics of viral research, but
| you'd think that with plenty of people out there willing to
| pay to cure themselves of HSV, or prevent it, there would
| be more financial support.
|
| Yet, the people working on the problem have as much funding
| as the YC Standard Deal announced this month. I wonder why.
| CommanderData wrote:
| I have an interest in this too, with most of the worlds
| population infected with some type HSV and being linked to
| Alzheimer's disease, MS and many horrible disease.
|
| It's about time we defeat HSV too!
| dnautics wrote:
| Well just be careful. If the disease is caused by latent
| virus in the brain triggering chronic inflammatory response
| in the brain creating ROS that degrade brain maintenance
| mechanism (which is a reasonable hypothesis) -- creating a
| stronger inflammatory response might accelerate the onset of
| the disease, not prevent it.
| el_benhameen wrote:
| Epstein-barr virus is in that same category of "lots of
| latent, lifelong infections that are maybe linked to a ton of
| age-related diseases in weird ways". No idea if it's a
| potential target, but would be pretty cool!
| drewcon wrote:
| Ask and you shall receive:
|
| https://www.umassmed.edu/news/news-
| archives/2022/01/phase-i-...
| el_benhameen wrote:
| Very cool!
| zionic wrote:
| I think we need to do a much better job at wiping out these
| "mostly benign" viruses. I suspect we'll someday learn they
| drastically increase your cancer risk, like we did with HPV and
| male throat cancer.
| [deleted]
| throwaway73838 wrote:
| Does anyone remember the French Nobel Prize winner who discovered
| HIV/AIDS saying that the SARS C19 had sections that appeared to
| be from the HIV virus?
| ceejayoz wrote:
| The same guy believes in homeopathy and that DNA can teleport
| via radio waves into a sample of pure water.
| https://en.wikipedia.org/wiki/DNA_teleportation
|
| It's a whole thing. https://en.wikipedia.org/wiki/Nobel_disease
| throwaway73838 wrote:
| It wasn't just him saying that. I once went on a forum for a
| journal article, and there were two camps of biologists -
| those speaking about the similar sections, and those refuting
| the claims. I noticed that most of the refutations came from
| scientists with Chinese sounding names. I realize that this
| is just anecdotal, and you can choose to believe me or not.
| But that's what I saw.
|
| You may still be able to find it on Google.
|
| Also, from the first para of his Wiki page:
|
| During the COVID-19 pandemic, Montagnier promoted the
| conspiracy theory that SARS-CoV-2, the causative virus, was
| deliberately created and escaped from a laboratory. Such a
| claim has been refuted by other virologists.[6][7][8][9] He
| has been criticised by other academics for using his Nobel
| prize status to "spread dangerous health messages outside his
| field of knowledge".[10]
|
| Looks like he's been at least partially vindicated.
| ceejayoz wrote:
| Other commenters have demonstrated it's readily findable on
| Google, and still bullshit. Paper withdrawn by its authors.
|
| > Looks like he's been at least partially vindicated.
|
| Did you cite the wrong paragraph?
| dr_zoidberg wrote:
| I remember headlines saying that, but the most I'm finding is
| that the paper that claimed such links was quickly retracted
| from bioRxiv[0]. I'm a bit lost as to how misinformation played
| in placing a Nobel Prize winner in the mix, possibly they
| mentioned there was research suggesting that link.
|
| [0] https://www.statnews.com/2020/02/03/retraction-faulty-
| corona...
| kahrl wrote:
| Luc Montagnier. Yes he's a quack now and yes he was immediately
| refuted.
|
| https://www.connexionfrance.com/French-news/Disputed-French-...
| hatware wrote:
| Good thing the medical establishment has lost all of my trust in
| the last 20 years. Even if this is a good thing, you're not going
| to have an easy time convincing me it is. The medical
| establishment has way too much control over things they should
| not, like governments.
|
| Profits over people is obvious. Trust is difficult to earn and
| easy to lose.
|
| I wish more of you folks had standards. At this point, I wouldn't
| care if Moderna or Pfizer came out with a totally legitimate cure
| to all cancers.
|
| The damage is done.
| gitfan86 wrote:
| I don't follow your logic. Because Fauci, Trump, Biden said
| things that turned out to be false, new medicines can no longer
| be created?
|
| Or are you saying that new medicines can still be created, but
| you will not take them out of spite toward the lies told during
| the pandemic?
| hatware wrote:
| If you don't follow my logic, I implore you to remember how
| life went on before 2019, and why the medical establishment
| has such a hold on the world for what has amounted to a cold
| virus that we must learn to live with. Just like pre 2019.
|
| It's time to start recognizing that the solutions to COVID-19
| did far more damage than COVID-19. Feel free to argue that
| "we have no idea how bad it would have been!"
|
| I assure you, we, _humans_, all made this worse than it had
| to be. It's time to stop the charade.
| gitfan86 wrote:
| That is fine if you think things would have worked out
| better if we just treated Covid like another strain of the
| flu. 99% of ER Doctors disagree with you. If you think
| their opinion doesn't matter, that is fine too, but I don't
| see why I should ignore their opinions and agree with
| yours.
| hatware wrote:
| spywaregorilla wrote:
| I would be happy if they cured cancer.
| hatware wrote:
| csee wrote:
| Industries cannibalizing themselves through competition is
| very common.
|
| If pharma was a monopoly, then they wouldn't want to cure
| cancer. But pharma isn't a monopoly, so the incentive then
| is to reduce the size of the pie as long as they get to eat
| the entire pie themselves.
| spywaregorilla wrote:
| It's a cute common conspiracy theory but it doesn't really
| hold up. Modern pharma is making progress all the time.
| E.g. as shown, an HIV vaccine.
| nsxwolf wrote:
| The conspiracy theory always ignores that cancer is a
| broad category. There will never be a single cure, but
| rather many individual cures. And the cures will really
| be more effective treatments that achieve remission very
| reliably. Most cancer treatments are already hypothetical
| cures, if things go well enough. The trick is to greatly
| increase how often it goes that well.
| hatware wrote:
| spywaregorilla wrote:
| Maybe, but modern pharma not being responsible for bad
| things wasn't the original claim.
| newsbinator wrote:
| Money aside, 1/3rd to 1/2 of their family members (and
| themselves) would then stop dying of cancer.
| msla wrote:
| So you think everyone working in the medical and
| pharmaceutical fields is an utterly amoral antisocial
| personality disorder case? Because that's what it would
| take for your conspiracy theory to work. If you honestly
| can't understand compassion, well...
| hatware wrote:
| That's rich. People are killing themselves, and tons of
| scheduled medical procedures are still being postponed.
|
| You'll reap what you sow.
| ineedasername wrote:
| How are human trials on high-risk low-incidence diseases like
| this conducted?
| jldugger wrote:
| > high-risk low-incidence diseases like this conducted
|
| If you're asking 'how do we test the vaccine without _trying_
| to give people HIV", one option is to give it to a lot of
| people, and record their outcomes over time.
|
| But first you need to prove the vaccine isnt like, super toxic
| in humans. So you do animal analog tests, then a limited test
| on humans, aka "Phase 1 trials". A previous article summarizes:
|
| > Moderna's vaccines passed Phase I testing earlier this year,
| which involves testing for safety using only a handful of human
| volunteers. Phase II tests for a vaccine's overall
| effectiveness, and with the move into Phase III, Moderna will
| be looking at its efficacy versus other prevention treatments
| currently on the market, such as pre-exposure prophylaxis, also
| known as PreP.
|
| - https://www.them.us/story/moderna-begins-hiv-vaccine-
| trials-...
| meepmorp wrote:
| That article may be wrong. According to clinicaltrials.gov,
| they were still recruiting for the HIV trial and the target
| completion date is April 11, 2023.
|
| https://clinicaltrials.gov/ct2/show/NCT05001373?id=NCT050013.
| ..
|
| Edited because my previous version was possibly wrong.
| jldugger wrote:
| Okay, well, it still outlines clinical trial phases
| correctly, right?
| meepmorp wrote:
| Oh, sure, it just seemed odd.
| ckarmann wrote:
| I am just speculating, but in many diseases like rabies and
| chickenpox you can give the vaccine after exposure to help the
| immune system fight the infection. It's because the period
| between exposure and symptoms is quite long, often more than a
| month for rabies for example.
|
| HIV can stay in the body for years before developing AIDS. So
| you can actually recruit people that have been tested positive
| recently and have not developed the disease.
| retrac wrote:
| While HIV is a relatively low incidence in the general
| population globally, there are some specific regions and
| subpopulations in various countries at much higher risk. In
| short, they mostly test HIV vaccines on young, single gay men
| in the West and young, single heterosexuals in South Africa,
| Tanzania, etc.
| f6v wrote:
| I guess the same as in diseases like tuberculosis. I've just
| read an article where they studied immune responses in recent
| TB infections. The authors recruited subjects from South
| Africa. I think it's not that hard to get them to join the
| trials since payout can be quite significant where such disease
| are widespread, especially compared to Europe or North America.
| And some areas have just outrageous HIV prevalence. Just sample
| a hundred people and you get a decent sample size.
| dogma1138 wrote:
| Why is the comment with the actual press release that honestly
| gives far better info flagged to death? @Dang can you fix this?
| adventured wrote:
| Interestingly their five link submissions are all dead as well.
| I'm guessing it was some kind of automated response based on
| the account history.
| mleonhard wrote:
| The them.us article [0] says:
|
| > but we'll be praying ... that by next year, LGBTQ+ communities
| around the globe will have a new reason to celebrate.
|
| This perpetuates the myth that HIV is mainly a problem for gay
| people. Can we change to another article, such as [1]?
|
| The Bill & Melinda Gates Foundation supports Moderna's HIV
| vaccine research [2].
|
| [0] https://www.them.us/story/hiv-aids-vaccine-human-trials-
| mode...
|
| [1] https://www.engadget.com/moderna-mrna-hiv-vaccine-
| trials-225...
|
| [2] https://www.modernatx.com/ecosystem/strategic-
| collaborators/...
| [deleted]
| bruceb wrote:
| More like it perpetuates the myth that LGBTQ+ is a monolithic
| group.
|
| HIV is more concerning for Gay men for a variety of reasons.
| There is nothing wrong with pointing out the obvious. Ask
| anyone who takes prep.
| TheSpiceIsLife wrote:
| Your comment perpetuates the myth that _gay men_ as a group
| are a homogenous whole.
|
| More specifically HIV, it's more of a concern for non-
| monogamous gay, and bisexual, men who engaging in unprotected
| anal intercourse.
| Throwaway24FGH wrote:
| missedthecue wrote:
| That seems like it's needlessly splitting hairs.
|
| _" STDs aren't a problem for humans as a group. They're a
| concern for people who have sex"_
| voz_ wrote:
| I don't understand how a fact is a myth?
|
| https://www.reuters.com/article/health-global-aids/men-with-...
|
| There is no shame in it, different diseases and viruses affect
| different people differently, because of different behaviors.
| It does not make Gay people worse, or better. It just means the
| actions they participate in, as a demographic cohort, is more
| likely to lead to an HIV infection when normalized for factors
| against another, non Gay, group.
|
| HIV has always been a huge thing in the gay community, and
| erasing that or trying to shift from that is an odd form of
| historical rewriting. Anyone who lived in SF during the HIV
| epidemic remembers this.
| s1artibartfast wrote:
| Men who have sex with men are vastly more likely to get HIV,
| but account for a minority of the annual infections globally.
| [1] Sex workers and customers make up a larger percent of
| infections. Most HIV infections occur in women opposed to
| men.
|
| I don't find the language particularly offensive, but I cant
| imagine them replacing LGBTQ+ in the sentence with sex
| workers.
|
| Then again, this is a publication for lbtq audiences, not sex
| workers.
|
| https://www.avert.org/global-hiv-and-aids-statistics
| fnordprefect wrote:
| It seems to be an LGBTQ-focused website, so it looks to be
| doing nothing more than viewing things from the viewpoint of
| (presumably) its biggest reader base...
| drocer88 wrote:
| https://www.cdc.gov/nchhstp/newsroom/docs/factsheets/cdc-msm...
| moooo99 wrote:
| > This perpetuates the myth that HIV is mainly a problem for
| gay people. Can we change to another article, such as [1]?
|
| But how is that a myth? The US Gov site [0] that is linked in
| the engadget article literally states that
|
| > HIV continues to have a disproportionate impact on certain
| populations, particularly racial and ethnic minorities and gay,
| bisexual, and other men who have sex with men.
|
| Fruther down:
|
| > Gay, bisexual and other men who have sex with men (MSM)b are
| the population most affected by HIV in the U.S.:
|
| > MSM accounted for 69% of new HIV diagnoses in the United
| States.
|
| While I agree that the focusing only on LGBTQ+ as a group is
| not an ideal way to put it, there is no myth in claiming that
| gay/bisexual men are at the highest risk of getting it.
|
| [0] https://www.hiv.gov/hiv-basics/overview/data-and-
| trends/stat...
| s1artibartfast wrote:
| This number changes dramatically when you look globally. MSM
| is about 23% of new infections
|
| https://www.avert.org/global-hiv-and-aids-
| statistics#footnot...
| miked85 wrote:
| It really isn't a myth though [1].
|
| [1] https://www.cdc.gov/nchhstp/newsroom/docs/factsheets/cdc-
| msm...
| vineyardmike wrote:
| The source appears to be a queer news source, so that's
| probably the reason behind the focus. HIV is certainly a major
| concern for the queer community.
| [deleted]
| Throwaway24FGH wrote:
| BiteCode_dev wrote:
| It's going to be 12 doses, you may still get aids, but a version
| that can be cured using bi-therapy instead of tri-therapy.
|
| But just like the COVID booster, after the 3rd shot, your chances
| of catching it increase the week after the injection.
|
| Who is going first?
| rubyist5eva wrote:
| > We could be getting even closer to stopping the spread of
| HIV/AIDS.
|
| Not if it's anything like the Covid-19 vaccines that don't stop
| someone from contracting or spreading it.
| echelon wrote:
| 70% prevention is better than 0%, and something tells me that
| it will see a much higher rate of adoption than the Covid
| vaccine.
| dogma1138 wrote:
| PREP already gives you good prevention for this to work it
| needs to be both a therapeutic vaccine at least at stages at
| which PEP is no longer effective as well and or as being at
| least as effective as PREP whilst being more cost effective
| as an overall treatment.
|
| Also there is no chance that this would have a higher
| adoption rate than COVID unless it turns out to give 100%
| life time immunity and would end up being part of the
| National vaccination program world wide.
|
| This likely would have the same usage as PREP/PEP today so at
| risk individuals and a post exposure treatment.
| adamrezich wrote:
| what makes you think so? how could the market for this be
| greater than the market for the covid vaccine? the number of
| people susceptible to covid is much greater than the number
| of people susceptible to HIV.
| yakshaving_jgt wrote:
| I think the general public's perception of the consequences
| of infection are different depending on the disease.
|
| I _think_ most people see it as "covid = bad cold; HIV =
| death".
| adamrezich wrote:
| but surely more people would say "my lifestyle choices
| mean that I'm never going to be exposed to HIV so I don't
| need a vaccine for it" than ditto for covid?
| yakshaving_jgt wrote:
| I think unprotected sex is more common than many people
| in wealthy countries realise.
| adamrezich wrote:
| sure but the set of all people who engage in frequent
| unprotected sex so as to be possibly susceptible to HIV
| is strictly smaller than the set of all people who could
| be possibly affected by covid.
| yakshaving_jgt wrote:
| Yes, it is.
|
| I'm not sure how we're lost in translation here, so I'll
| try to express this another way.
|
| I think the majority of sexually promiscuous adults
| aren't particularly concerned about COVID infection,
| because the likelihood that they'll die from it is low.
| If they do catch it, they will most likely recover
| without long-term damage.
|
| I think those same adults however are indeed concerned
| about HIV infection, because it is [so far] incurable,
| and has an enormous social stigma attached to it, and
| without constant treatment will eventually kill you.
|
| The number of people who would benefit from a drug
| against COVID is larger than those who would benefit from
| a drug against HIV, _however_ , of those who would buy
| either drug, I think the latter drug is the one that
| would have much higher market demand because of just how
| consequential an infection with that disease is.
| adamrezich wrote:
| well, hopefully that market demand results in getting a
| drug that is more than adequate at what it's supposed to
| do, because I'd imagine the consequences would be much
| worse.
| iqanq wrote:
| gameswithgo wrote:
| The covid-19 vaccines were very effective at preventing disease
| and spread until the omicron mutation, which perhaps wouldn't
| have happened if not for vaccine hesitancy. (but that is an
| inevitable human nature thing, so you have to accept it and
| deal with)
|
| Fortunately the vaccines were still very effective at
| preventing death and hospitalization with omicron, I wonder how
| many lives were saved overall, so far? It is really quite
| remarkable.
|
| Given the slower way HIV spreads we have a much better chance
| at actually getting rid of it. Its not flying around in the air
| mutating in a billion people at once every day.
| vkou wrote:
| > The covid-19 vaccines were very effective at preventing
| disease and spread until the omicron mutation, which perhaps
| wouldn't have happened if not for vaccine hesitancy.
|
| I'm happy to piss in the coffee of vaccine hesitants any day
| of the week (point me to the mug), but we can't blame the
| variants on vaccine hesitancy.
|
| Both delta and omicron originated in unvaccinated populations
| in the developing world, where the problem is not vaccine
| hesitancy [1], but the lack of _availability_ of vaccines
| [2].
|
| [1] Delta arose before any vaccines were approved, and yes,
| of course, there's vaccine hesitancy in South Africa, but
| there's also, simply put, not enough vaccines to go around.
|
| [2] For some mysterious reason, our economic planners thought
| that getting the developed world inoculated in 2021, and the
| developing world in 2022 was a smart plan. It wasn't, but now
| we're reaping the consequences of it. I eagerly await the
| next variant.
| sharikous wrote:
| ... and yet the HIV virus is notoriously terribly difficult
| to develop a vaccine against. It mutates easily and you don't
| have a natural antibody response that is easy to trigger.
| Like one of the top comments I really wish some expert would
| enter the discussion and explain what exactly are our
| expectations.
| dbsights wrote:
| Come on, this isn't true. Even with delta the waning efficacy
| had become obvious in those countries that vaccinated early,
| with all time high infections in jurisdictions that were
| virtually completely vaccinated (e.g. Israel, Waterford). One
| study estimated 211 days until protection vs infection was
| statistically indistinguishable from someone who was not
| vaccinated (https://papers.ssrn.com/sol3/papers.cfm?abstract_
| id=3949410).
|
| And how can you possibly speculate that a vaccine evasive
| mutation is the fault of the unvaccinated? While we can only
| guess, the evolutionary pressure is obvious: a vast number of
| hosts available to the first variant that can defeat the
| narrow immunity against the spike protein. We created a
| monoculture, with all the attendant risks.
| Vrondi wrote:
| But, HIV mutates super easily, which is why we do not already
| have a more traditional vaccine that works. It will be a
| greater challenge in this regard than COVID-19/Omicron, not
| an easier one.
| woodruffw wrote:
| Two observations:
|
| 1. Given the continued efficacy of the COVID-19 vaccines
| against severe illness, it stands to (lay-)reason that a
| similar outcome might occur with HIV. A world in which HIV
| is roughly as transmissible as it currently is (and is
| still responsive to other avenues of treatment/prevention,
| like PrEP) but where it does not cause fatal
| immunocompromization is an _extremely_ preferable world.
|
| 2. We have no particular reason to believe that HIV's
| mutation vectors are more or less susceptible to the
| vectors that mRNA vaccines target, versus "traditional"
| vaccines.
| pokot0 wrote:
| As much as I'd like to blame them, the number of people who
| willingly refused the vaccine are irrelevant compared to
| those who do not have access to it.
| tamcap wrote:
| This is a valid point, but I think ignores amount of public
| health resources "spent" on trying to address vaccine
| hesitancy and healthcare resources addressing "unnecessary"
| hospitalization and complications.
|
| Now imagine we could cut the above in half, and then use
| some fraction of those savings (as a nation) promoting
| wider adoption of vaccines globally. If we've reached
| higher levels of vaccination earlier (in the USA), more
| people without access to the vaccine currently would've
| been able to get it.
| thebradbain wrote:
| HIV doesn't mutate in the same way a disease like Covid
| does, at least not at the same speed-- also, PrEP has
| existed for years. It's still proven to be effective
| protection against contracting HIV even if directly exposed
| (though it's a pill that must be taken every day rather
| than a vaccine).
|
| I honestly don't know why everyone who is sexually active
| isn't on PrEP (the federal government even mandates it be
| free to those without insurance in most cases)-- it should
| be as common practice as wearing a condom and birth
| control, yet its existence isn't even known to many people
| (especially among straight people).
| [deleted]
| thesis wrote:
| Not sure why you're being downvoted all much... well actually
| no it's pretty obvious.
|
| I think you're right though. The current Covid-19 vaccines are
| proven to lose efficacy over time. Will the same thing happen
| with this one as well? It's a good question.
| luckydata wrote:
| because the point he's making is wrong. Vaccines are doing a
| fantastic job at slowing down the progression of the virus
| which is key to keep mutations at bay. No vaccine is 100%
| effective, but even 80% effectiveness radically changes the
| dynamic of a pandemic, it's so easy to see that I don't
| understand what can lead someone to deny this fact besides
| bad faith.
| kbos87 wrote:
| Exactly. The COVID vaccines have been proven over and over
| again to reliably prevent serious illness across the
| original strain and every variant of concern we've seen
| since then. The fact that they initially also largely
| prevented infection against the original strain was a bonus
| that scientists were never counting on.
|
| Now, just because omicron is better at driving breakthrough
| infections, that fact is being used in bad faith by some
| who now say the vaccines "don't work", even though they are
| still as effective at preventing serious illness
| firmnoodle wrote:
| I think you may want to revisit your 80%. The vaccine
| efficacy for sterilization of the virus ended up dropping
| more quickly than expected and that's even with pre-Delta
| variants. Look at the Israel data. When you don't
| understand, I suspect what you are encountering isn't bad
| faith actors, but more informed people.
| csee wrote:
| But here you're talking about efficacy against infection
| and mild disease, which is not so relevant if we're
| talking about preventing new strains. New strains are
| thought to evolve in immunocompromised people with high
| viral loads over long periods of time, which allows both
| many mutations to occur as well as for those mutations to
| become dominant. So I believe the question should be to
| what extent the vaccines help prevent serious disease in
| people with comorbidities - and the answer is that they
| help to a great extent (whether 70% or 90%).
| hn_throwaway_99 wrote:
| I wholeheartedly agree, I downvoted the comment because it
| appeared to be made in bad faith (and from another comment
| I posted on this topic, I obviously share the concern that
| this HIV vaccine may lose efficacy over time).
|
| Also, it's not hard to see how a vaccine for HIV would be
| _much_ more effective at slowing pandemic progression than
| a vaccine for an airborne virus, even if the vaccines
| conferred the same benefits. Right now, if you get HIV, you
| are essentially contagious for life until you get on
| antiretrovirals that can bring your viral load to
| undetectable (and, you also need to be on those
| antiretrovirals for life). If an HIV vaccine prevented you
| from having a long term infection, it _could_ potentially
| fully end the pandemic.
| solarkraft wrote:
| > well actually no it's pretty obvious
|
| If you think they're right you may not understand why the
| comment is being down voted.
|
| > The current Covid-19 vaccines are proven to lose efficacy
| over time. Will the same thing happen with this one as well?
|
| Like with any vaccine: Probably.
|
| > It's a good question
|
| It's pretty besides the point. To recycle my car brakes
| analogy: They also lose efficacy over time, yet are widely
| considered to be useful.
| missedthecue wrote:
| I think it's just the speed at which it has happened
| though. Most children born in developed countries today
| receive a slew of vaccines which will provide immunity to
| catching those diseases for decades. It's discouraging that
| we're looking at shot no. 4 for the mRNA covid vaccines
| within a year and a half, and despite even that, infection
| rates are still very strong.
| techdragon wrote:
| Thanks for the breaks analogy, it's one I intend on using
| when talking to people I. The real world. It's a good one
| given how basically everyone has either dealt with or
| understands this basic yet essential car maintenance issue
| and the nature of the appropriate response.
| peteradio wrote:
| Car brake dust is an extremely potent carcinogen, take care
| when dealing with them.
| snovv_crash wrote:
| At least they don't make them from asbestos anymore.
|
| My dad tells me about taking shop class in high school,
| and they'd be sanding down asbestos brake pads with an
| angle grinder to remove the high spots to prevent
| glazing. No masks of course.
| perardi wrote:
| ...or it totally could, if it primes T-cells to fully clear the
| infection, or keep it to such a low level that the viral load
| is minimized.
|
| HIV has a tremendous latency period. It lurks for a long time
| before symptom onset. If a vaccine _doesn 't_ provide
| sterilizing immunity, but _does_ prime T-lymphocytes to clear
| the virus, or keep it to an extremely low viral load, it would
| make people _substantially_ less likely to spread the virus, or
| have symptomatic progression to AIDS.
|
| This is, of course, easier said than done.
|
| https://www.aidsmap.com/about-hiv/search-hiv-prevention-vacc...
| solarkraft wrote:
| Car brakes are also ineffective because they don't prevent 100%
| of collisions, huh?
| erglkjklrh wrote:
| luckydata wrote:
| There's a difference between "someone" and "no one" and
| "everyone". Someone with an engineering education should be
| able to understand that very easily, it's a shame you don't.
| tehjoker wrote:
| No one in this thread knows anything about vaccines or
| infectious disease. Each organism is different and requires a
| detailed understanding to see what the potential for the
| vaccine is. You can't just take COVID-19's performance and
| project that onto another disease. mRNA allows the targeting of
| specific proteins. The efficacy of the T-cell and B-cell
| responses are going to be highly dependent on that protein's
| structure, its importance and level of conservation in the
| pathogen, and other factors.
|
| COVID-19 seems to require a persistently high level of
| neutralizing anti-bodies and the T-cell response seems to be
| less important (and also plays a role in auto-immunity). On the
| plus side, the wild-type vaccine has continued to be fairly
| effective against even highly mutated Omicron which is
| surprisingly good even if strategically, it is suboptimal that
| the virus has continued to mutate and evade the vaccine to ever
| greater degrees.
| Ekaros wrote:
| I would be really worried with false sense of security when
| dealing with HIV/AIDS... Covid in the end is a mild thing, same
| can't really be said about HIV/AIDS. And if the protection is
| only temporary and partially it might be worse than having
| nothing at all if it leads to lot more risk taking.
| megaman821 wrote:
| The Covid-19 vaccines were made against the original strain in
| which it was 95% effective. Let's see how the updated Omicron
| vaccine goes. I am guessing we are going to see above 90%
| effectiveness. mRNA vaccines are looking pretty promising at
| neutralizing the specific virus they are targeting. How
| effective that is for mutated and related viruses is what
| remains to be seen.
| marcosdumay wrote:
| > How effective that is for mutated and related viruses is
| what remains to be seen.
|
| I imagine that depends much more on the virus than on the
| vaccine.
| megaman821 wrote:
| Wouldn't it depend more on how well-chosen the target
| protein is? If it mutates too fast the vaccine won't be as
| effective. This says nothing about the effectiveness of the
| mRNA technique though, which seems to reliable induce an
| immune response to the target protein.
| pabl8k wrote:
| it's defense in depth.
|
| if someone has HIV, they can be treated and if they are
| consistent with treatment they can have such a low
| (undetectable) viral load that it is not transmittable. (aka
| U=U)
|
| additionally, high risk populations (transactional sex, msm,
| intravenous drug users) can take the same drugs and be
| protected from the virus. (aka PREP)
|
| also people with known exposures or likely exposures can have
| post exposure prophylaxis with the same drugs (e.g. in the case
| of an accidental needle stick in a healthcare worker).
|
| These defenses have already radically slowed the spread and
| increased the lifespan and quality of life of those who become
| HIV positive.
|
| Now we will hopefully have a an additional defense that will be
| even easier (no daily dosing required for negative at-risk
| population) and probably much more broadly administered.
|
| I love the progress we are making with vaccines.
| ukie wrote:
| unnouinceput wrote:
| ipnon wrote:
| It seems like HIV is mainly contracted by gay men in the First
| World, drug users in the Second World, and straight people in
| the Third World. It does seem a strange shoutout, but I imagine
| they are already prepping the ad campaigns for the West where
| they'll make the most money selling this vaccine.
| [deleted]
| tacLog wrote:
| It's important to remember that any community can spread it.
| Needle sharing among intravenous drug users comes to mind.
| However, you can't deny that HIV has struck a generational blow
| upon the LGBTQ+ community.
|
| If this works it will be the end to an era of fear. Many will
| remember those that where lost and wish this only happened
| sooner. A new reason to celebrate is underselling the impact
| this will have.
| ipnon wrote:
| It seems to me like lumping lesbians and the queer into this
| calculus is a little insensitive because it was almost
| exclusively gay men and trans women who bore the brunt. I'm
| sure this press release ran by a publicist who said, "we have
| to use all the letters or else we'll get torn to shreds on
| Twitter."
| tacLog wrote:
| I get what your saying.
|
| But on the other hand we are just talking about celebrating
| this. I feel like those sub-communities are probably more
| aware of the impact HIV than the average cis straight
| person and are probably going to celebrate this as well.
|
| I don't get what's insensitive about it at all so maybe I
| am missing your point.
| ipnon wrote:
| If we get down to brass tacks, this is a situation where
| sex takes precedence over gender. The HIV epidemic in the
| West was borne by XY people, and the history of HIV in
| America is by and large an XY history. What are we
| obfuscating by painting this history with a broadly
| "queer" brush?
| [deleted]
| orra wrote:
| Obviously cis het people can spread HIV. But the AIDS pandemic
| was absolutely brutal--devastating--for a generation of LGBT
| people, especially gay men.
| [deleted]
| RcouF1uZ4gsC wrote:
| I think that this might be a follow-on benefit of Operation Warp
| Speed which had a post a few days ago.
|
| From that post, it seems like one of the benefits to Moderna
| (apart from a big cash infusion) was that Moderna had the
| science, but did not actually have the experience and pipelines
| of actually bringing a drug to a broad market. They did not have
| the experience and infrastructure for large scale human trials
| and for the large scale manufacturing.
|
| Experience with creating, testing, manufacturing, and rolling out
| the Covid vaccines, were I am sure invaluable in helping Moderna
| become a "full-stack" drug company.
|
| Very excited by this development and looking forward to
| (hopefully promising) results.
|
| It will be wonderful if we can make HIV/AIDS something future
| generations will only know from history books.
| egrlk45ylkj wrote:
| localhost wrote:
| Last night I read this Nature review paper [1] and this history
| article [2] that describe the parallel investigations in both
| mRNA technology and lipid nanoparticle technology that ultimately
| led to the development of mRNA based vaccines. As we come up on
| Nobel Prize season, the second article is particularly
| interesting if you want to get a preview of some of the possible
| recipients.
|
| [1] https://www.nature.com/articles/s41578-021-00358-0 [2]
| https://www.nature.com/articles/d41586-021-02483-w
| pwned1 wrote:
| Since the mRNA covid vaccines seem to only work for 90-180 days,
| why would a vaccine for anything else be different?
| 535188B17C93743 wrote:
| I don't know anything about vaccines or their validity, but
| even then, the current solutions are a shot once a month or
| PrEP every day... so twice a year sounds pretty great to me?
| thehappypm wrote:
| AIDS and COVID are extremely different.
|
| If you are exposed to COVID but got the vax a year ago, you're
| likely to have symptoms. You probably don't actively have
| antibodies. But that's okay! You might have some symptoms, in
| fact they might be severe, but given enough time your immunity
| will ramp back up, and you still will clear the virus.
|
| If you clear HIV after a week or two, that is a HUGE win for
| you.
| NoblePublius wrote:
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