(C) PLOS One This story was originally published by PLOS One and is unaltered. . . . . . . . . . . A Mini-Surge of Clinical Trials and Advances for People with Immunosuppression (NextGen Covid Vax Update 18) [1] ['Hilda Bastian'] Date: 2024-06-30 It’s been a slow month for reporting of results, but a big one for new trials and for potential improved vaccine boosters for people with immunosuppression. There are 2 new trials registered – one for an intranasal vaccine from the US NIH’s NIAID, and one for an mRNA vaccine aiming to be more effective and more durable for people with immunosuppression or immunocompromise in Australia. Plus, we heard that US Project NextGen is funding another couple of phase 2b “mini-efficacy” trials – one for another vaccine aiming to provide better protection to people with immunosuppression, and another intranasal vaccine. That brings the number of mucosal Covid vaccines reaching clinical trial to 29. In other trial news, we also heard that one more phase 1 trial of a pancoronavirus vaccine has fully recruited. And in this update, I’ve also added 4 reports of preclinical studies, for 3 vaccines. As usual, I have the news from the last month broken down into 3 categories of next-generation Covid vaccines (definitions below). Each of these sections ends with an overview of vaccines in the category. Mucosal vaccine development news Durable or “variant-proof” vaccine news Pancoronavirus vaccine news Addendum 1: List of authorized vaccines (with countries) Addendum 2: Table of mucosal vaccines in clinical trials Addendum 3: Table of pancoronavirus vaccines with results Addendum 4: Definitions of vaccine types Mucosal vaccine news This month, the 29th mucosal vaccine for Covid headed into clinical trial, and US Project NextGen funded a phase 2b “mini-efficacy” trial for another intranasal vaccine. That brings the total they have funded in this category to 4. All but one have reported they plan to get started in 2024, with one recently saying if they start soon, then interim results could theoretically be available early in 2025. In each of these trials, the vaccine will go head-to-head with mRNA vaccine in 10,000 participants. Another mucosal vaccine goes into clinical trial in the US This vaccine is being developed by the NIH’s National Institute of Allergy and Infectious Diseases (NIAID). A viral vector vaccine, it’s based on murine pneumonia virus. The developers have published 2 preclinical studies for this vaccine, both in primates. The first study tested a single dose in macaques. In the second report, they tested 2 doses, and found that 3 out of 4 macaques did not get infected in a SARS-CoV-2 challenge, while all the control animals did. The phase 1 trial is testing intranasal administration, in 3 different strengths. They planned to start recruiting 60 people this month, in Georgia, New York, and Texas. Another mucosal vaccine gets ProjectNext Gen funding for a 2b “mini-efficacy” trial This vaccine is an intranasal viral vector vaccine based on PIV5 (parainfluenza 5), developed by the University of Georgia with CyanVac. The vaccine has been in a phase 2 trial with 227 participants in the US. The developers provided some information about their phase 1 trial in a press release early this year. They plan to start the Project NextGen-funded phase 2b trial in US fall. New preclinical results: I’ve added 2 preclinical reports on results for mucosal vaccines to my collection since the last update: Wuhan Institute of Virology and Shenzhen Instititute of Advanced Technology (China): This is an intranasal protein subunit vaccine, tested in mice. It aims to be variant-proof. Division of Respiratory Virus Vaccines, National Institutes for Food and Drug Control, Beijing (China): This is an intranasal protein subunit vaccine, tested intranasally and intraperitoneally in mice. Mucosal Covid vaccine overview 5 mucosal vaccines are currently authorized for use, at least 1 in each of 6 countries. However, none have been authorized by a drug regulatory agency designated stringent, or listed, by WHO. 29 mucosal vaccines have reached clinical trial, although some of the vaccines are no longer in development. The vaccines that have entered clinical trials are tracked in a table below. In addition to the 5 authorized mucosal vaccines, 4 have reached phase 2 trials, and another 2 have reached phase 2/3 trial. US Project NextGen-funded trials in this category: Project 2b (“mini-efficacy”) for the intranasal protein subunit vaccine from Castlevax (planned to start in the last quarter of 2024); Project 2b for the intranasal live attenuated vaccine from Codagenix; Project 2b for the oral viral vector vaccine from Vaxart (planned to start in 2024, possibly in US summer); and Project 2b for the intranasal viral vector vaccine from CyanVac (planned to start in 2024, in US fall). None of these trials has been registered at ClinicalTrials.gov as yet. Back to contents Durable or “variant-proof” vaccine news This month, there’s news for 2 vaccines aiming to provide boosters that are more effective and more “variant-proof” for people with immunosuppression. GEO-CM04S1 from GeoVax (USA): This is a viral vector vaccine, based on modified Ankara virus (MVA). It was developed at the City of Hope with the NIH’s National Cancer Institute (NCI), to better serve immunocompromised people on cancer treatment. Results released so far for this vaccine have been encouraging. For example, the developers previously published data for 13 participants with blood cancer, a subgroup of participants in a phase 2 trial. My previous summary on this: Their immune responses were similar or superior to those of healthy people receiving the vaccine and healthcare workers vaccinated with the BNT/Pfizer vaccine. And people were still showing signs of immunity after 6 months. This month, GeoVax announced that they have received funding from Project NextGen to run a 10,000-participant phase 2b “mini-efficacy” trial. No word yet on timing for this. This vaccine already has 3 ongoing phase 2 trials. In a recent company overview, a slide about GEO-CM04S1 mentioned that it was durable against variants for more than 12 months, but the data on this haven’t been published as far as I know. (Records in my collection for this vaccine here.) HN-0001 from HelixNano (USA, Australia): This is an mRNA vaccine, and a phase 1 safety trial of a booster dose in 48 healthy people has been registered in Australia; a group of people in this trial were registered separately. It includes a comparison group of people being vaccinated with the BNT/Pfizer vaccine. I’ve included this vaccine in this category because early in the pandemic, a company spokesperson said they were trying to develop a “mutation-resistant” vaccine. This year, when they got the green light for a phase 1 trial, a company spokesperson described the vaccine as “a second-generation COVID-19 mRNA vaccine candidate specifically designed to prevent COVID-19 in immunosuppressed and immunocompromised populations.” Other news: There’s a bit of news for the vaccine from Tonix (USA), a company funded by Project NextGen to run a phase 1 trial. The developers gave a poster presentation this month. I don’t think the data on their Covid vax is new, but I didn’t scour through to be sure. However, the poster reiterates their plan to go into clinical trial this year. (The poster could be worth looking at if you’re interested in a technical overview of the platform, and why this pox-based vaccine platform is aiming for lifelong immunity from a single dose.) Finally, the only preclinical report I added for this category of vaccine is the one for a mucosal vaccine already mentioned above (from the Wuhan and Shenzhen Institutes). Durable or “variant-proof” vaccine overview Note: This is a rather vague category, including vaccines that aim to be more durable. I’m not sure how many can be classified as aiming to be “variant-proof”. Authorized vaccine: There is one vaccine in this category that has been authorized by a drug regulatory authority designated by WHO has stringent, or listed – and tested against an mRNA vaccine: LUNAR-COV19 (USA): This self-amplifying mRNA vaccine was authorized in Japan in November 2023. US Project NextGen-funded trials in this category: Phase 1 for TNX-1800 from Tonix (aiming for lifelong immunity) (planned to go into clinical trial in 2024); Phase 2b (“mini-efficacy”) for Gritstone Bio (self-amplifying mRNA). Phase 2b (“mini-efficacy”) for GeoVax (viral vector vaccine). These trials have not been registered at ClinicalTrials.gov as yet. Back to contents Pancoronavirus vaccine news Pancoronavirus vaccines aim to provide protection not only from variants of the SARS virus that causes Covid, but also against the next new coronavirus to spread among humans. Clinical trial news: There are 4 of these vaccines in phase 1 clinical trials, and one in a phase 1/2 trial. This month, the developers announced that the phase 1 trial of the protein subunit vaccine from Osivax in France has fully recruited, with 48 participants. They had begun recruiting for the trial in February, and expect to get first results this year. This vaccine aims to provide protection to the subgroup of coronaviruses that include the ones causing Covid and the original SARS. New preclinical results: This month, I added 2 preclinical reports for a vaccine that’s new to my collection – one report from this month, and one I had missed in 2022. The vaccine, called SARS2-S, is being developed in the US by researchers at Georgia State University and the University of Iowa. The developers have been testing 2 versions of their mRNA vaccine, and this new report shows how they settled on which to keep working on. This version of the vaccine includes a component of the virus that causes the Covid Omicron variant, with a part of it replaced with the equivalent component of the original SARS. In the first part of the study, vaccinated and control mice were challenged with the Omicron variant of the virus, and the original SARS. Omicron isn’t life-threatening to these mice, so the developers measured signs of infection for the Omicron challenge test. Signs of immune response were high for the vaccinated mice. All the mice injected with the SARS-containing version of the vaccine survived the SARS challenge, and didn’t lose weight – whereas 40% of the control mice died, and weight loss was high among survivors. Then, another group of mice were injected with serum from either vaccinated or control mice, and challenged with the original SARS virus. Signs of immune response were high for mice vaccinated with the SARS-containing-version. Pancoronavirus vaccine overview A table below this post keeps track of vaccines I’ve added to this category so far that have publicly available preclinical results. There are 5 of these vaccines in phase 1 clinical trials, with some results for 2 of them marked *: DIOSynVax (Cambridge University spin-off, UK) – mRNA. INSERM/LinkInVax (France) – protein subunit. Osivax (France) – protein subunit (phase 1 trial fully recruited in June 2024). * VBI Vaccines (Canada) – eVLP. * Walter Reed Army Institute of Research (WRAIR, USA) – protein subunit. Back to contents Addendum 1: List of authorized next generation Covid vaccines (with countries) There are now 7 next-generation Covid vaccines authorized in 7 countries. Only one has been authorized by a drug regulatory agency designated stringent, or listed, by WHO – it’s in bold. I’ve listed the vaccines in 2 categories, in order of date of first authorization. Mucosal: Razi-Cov Pars (Iran), intranasal protein subunit vaccine: Iran (October 2021). Sputnik (Russia), intranasal viral vector vaccine: Russia (April 2022). Convidecia (China), inhaled viral vector vaccine: China (September 2022), Morocco (November 2022), Indonesia (March 2023). iNCOVACC (USA/India), intranasal viral vector vaccine: India (September 2022). Pneucolin (China), intranasal viral vector vaccine: China (December 2022). Self-amplifying mRNA: Gemcovac (India): India (June 2022). LUNAR-COV19 (USA): Japan (November 2023). Back to contents Addendum 2: Table of mucosal vaccines in clinical trials * Indicates new entry since previous update post. Note: Where there is a link to “All records” for a vaccine, that’s in my public Zotero collection for the vaccine, and it may include non-mucosal studies for that vaccine. Notes on that collection are here. For details on how I track Covid vaccine progress to maintain that collection, see my background post. Back to contents Addendum 3: Pancoronavirus vaccines with preclinical results * Indicates new entry since previous update post. Back to contents Addendum 4: Definitions of vaccine types Mucosal vaccines: These enter the body the way the virus does – through mucosal tissues. It’s hoped that provides defence against infection. They can be administered via different routes – squirts or drops in the nose, inhaled through the mouth through a nebulizer (similar to an asthma medication), or in tablet, capsule, or sublingual form. Pan-SARS-CoV-2 or “variant-proof” vaccines: These aim to provide protection against any variant of the coronavirus that causes Covid-19 – including future variants. I include vaccines that aim for greater durability in this group. Pancoronavirus can be targeted to: the “subgroup” the 2 SARS viruses came from (the sarbecovirus subgenus), coronaviruses from the next level up (the genus, betacoronavirus, which includes lethal diseases like MERS, as well as common cold viruses), or the whole coronavirus family – it has 4 genuses, including betacoronavirus and alphacoronavirus (with more common cold viruses). I classify a vaccine as a pancoronavirus one when the developers are explicitly targeting coronaviruses more broadly than SARS-CoV-2, and have tested for signs of response to non-SARS-CoV-2 coronavirus(es) (or clearly plan to). Back to contents You can keep up with my work at my newsletter, Living With Evidence. And I’m active on Mastodon: @hildabast@mastodon.online ~~~~ For details on how I track Covid vaccine progress, see my background post. Notes on my collection of studies are here. The collection is in a public Zotero library you can dig into here. Previous update posts on next generation Covid vaccines: 17. Next generation (May 2024) All my Absolutely Maybe Covid-19 vaccine posts All previous Covid-19 posts at Absolutely Maybe My posts at The Atlantic, at WIRED, and debunking posts at my personal website. Disclosures: My interest in Covid-19 vaccine trials is as a person worried about the virus, as my son is immunocompromised: I have no financial or professional interest in the vaccines. I have worked for an institute of the NIH in the past, but not the one working on vaccines (NIAID). More about me. The cartoon is my own (CC BY-NC-ND license). (More cartoons at Statistically Funny.) 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