(C) PLOS One This story was originally published by PLOS One and is unaltered. . . . . . . . . . . More Next Generation Covid Vaccines Are Heading Into Clinical Trials (Update 10) [1] [] Date: 2023-08-25 This month, we got news that another couple of next generation vaccines are heading into human trials, both with national research agency support – an intranasal vaccine from the US, and a pancoronavirus vaccine from France. The US government’s Project NextGen announced that a billion dollars is available to support a network of vaccine trials. And according to a company report, the first public results for a clinical trial of a pancoronavirus vaccine could be around the corner. Those highlights and more below, broken down into news on US Project NextGen, and 3 categories of next-generation Covid vaccines (definitions below). Update on US Project NextGen Mucosal vaccine news Covid-19 “variant-proof” vaccine news Pancoronavirus vaccine news Addendum 1: Table of mucosal vaccines in clinical trials Addendum 2: Table of pancoronavirus vaccines with results Addendum 3: Definitions of vaccine types Update on US Project NextGen First, a recap. In May, the US government-funded Project NextGen was announced, with US$5 billion for public partnerships to develop better Covid vaccines and treatments (more on this in my June update). At the end of June, journalists reported that about 70 companies had responded (not only on vaccines). Back then, it was expected that there would be eventually be support for early-to-mid-stage clinical trials of up to 10 vaccines, with shared protocols and systems. The first funding recipients were announced earlier this week, although we still don’t know which vaccines are likely to get the boost. US$1 billion was awarded to 4 companies that run clinical trials, to be ready to run phase 2b vaccine trials. The aim is to “speed the development of new vaccine candidates, providing a network of at-the-ready trials with the flexibility to pivot to the most promising new vaccines as they mature. The public can expect to see clinical trials for new vaccine candidates targeting longer-lasting protection against future variants as early as this winter under Project NextGen.” Phase 1 trials are first-in-human trials, testing safety and helping establish dosages. Phase 2 trials are mid-stage – bigger than phase 1, but not as big as a phase 3 trials for establishing efficacy. Phase 2b trials are small efficacy trials, midway between phases 2 and 3. That means Project NextGen isn’t going to get a vaccine all the way through to FDA approval: Manufacturers will need to do that bit of heavy lifting. What vaccines could be ready for phase 2b in the US by the end of year? There are more than half a dozen mucosal vaccines from US developers that are at least as far along as fully-recruited phase 1 trials in the table below. There’s not enough published data from most of them though, so it’s hard to know which might be going well enough to justify an efficacy trial. Nor do we know which groups want to run their trial with Project NextGen. One stands out, though – NDV-HXP-S, the vaccine that inspired the cartoon at the head of this post. It’s developed at Mt Sinai in New York, and is available non-profit for development in lower income countries – 4 have used it. Some background on this vaccine (from a previous post): It couples old school, widely accessible technology – the vaccine can be mass-produced in eggs the way flu vaccines are – with a major advance in the way the virus spike is modified. It’s a viral vector vaccine based on the Newcastle Disease virus (NDV) and the Hexapro spike (HXP-S), which is a modification of the spike protein that could make this vaccine particularly potent. A license from the University of Texas at Austin developers of HXP-S is available to low and middle countries without royalties, and the Mt-Sinai-developed NDV platform is also non-profit. There’s a must-read article on this vaccine by Carl Zimmer in the New York Times. Last year, Mount Sinai announced the formation of Castlevax to develop this vaccine commercially. Although we’ve only seen press release reports for them, there are phase 1 trial results for an intranasal version in the US, as well as phase 2 trial results for the intranasal version developed in Mexico. It’s not the only possibility, but it’s definitely one to look out for in the news. Back to contents Mucosal vaccine news One of the vaccines headed into clinical trials is an intranasal vax developed by the US National Institutes of Health (NIH). The development was announced by Dartmouth, who will be working on the vaccine and its trials, and Exothera, a manufacturer from Belgium that has been commissioned to produce enough of the vaccine for the trials. The trials will be phase 1/2, in Africa and the US. Researchers at the NIH have been involved in the development of several vaccines with published results, but I haven’t been able to pin down for sure which vaccine this is – or if anything has been published about it. The Exothera press release says it’s based on adenovirus 4, but also mentions live, non-replicating virus. I’ll be on the lookout for more details. Someone on Mastodon, whose post I lost track of (apologies!), alerted me to a media report in the US that developers of the University of Washington St Louis (WUSL) intranasal vaccine expect it to “be ready to be presented to the FDA in the United States by the end of the year.” I’m not sure what that means, but it seems to me it could be early steps in the process, not an application for approval. This vaccine is an adenoviral vector vaccine, developed in the US under the name ChAd-SARS-CoV-2-S. It was used by Bharat Biotech in India to develop a vaccine called iNCOVACC there – authorized for use there in September 2022 (making it the third mucosal vaccine to be rolled out globally). However, the amount of trial evidence accepted in India isn’t necessarily going to be enough in the US. Bharat Biotech published results of their phase 3 trial this month – in January, those results were released in a preprint, so it’s been included in the last few updates here. We’re still waiting to hear from the FDA on specific requirements for approving Covid vaccines – the emergency use authorization expires later this year. I had a look at the most recently FDA-approved vaccine for non-pregnant adults: That was approved with a placebo-controlled phase 3 trial with 25,000 participants. The phase 3 trial for iNCOVACC had only around 3,000 people, with fewer than 200 in a control group. This month, the developers from WUSL released a fourth report of preclinical results. In that study, hamsters vaccinated with ChAd-SARS-CoV-2-S were in contact with both vaccinated and unvaccinated hamsters. The developers concluded that while the intranasal vaccine didn’t completely stop virus transmission, it had the potential to interrupt transmission – the animals that showed signs of the virus didn’t have a high enough viral load to transmit it to others in turn. (This vaccine is listed in the table below as BBV154 (iNCOVACC).) Back to contents Covid-19 “variant-proof” vaccine news I didn’t see new developments or results for vaccines in this category. Gritstone Bio reported to investors, however, that they expect to release more results from their phase 1 trials later this year. This is a self-amplifying mRNA vaccine that has 3 phase 1 trials in progress, including with some NIH funding. More on what we know so far in my Update 8. Back to contents Pancoronavirus vaccine news As far as I know, there are still only 3 vaccines in this category in phase 1 trials: an mRNA vaccine from DIOSynvax (Cambridge University, UK); a virus-like particle vaccine (eVLP) from VBI Vaccines (Canada); and a protein subunit vaccine from the Walter Reed Army Institute of Research (USA). A VBI Vaccines company report said they expect to have interim results of their phase 1 trial by the end of September – if so, that’s the first time we’ll see trial results for a pancoronavirus vaccine. As mentioned above, a fourth pancoronavirus vaccine is heading into a phase 1 clinical trial, expected to start in early 2024. Developed by France’s INSERM, the national health and medical research institution, it has now been named PanCov. INSERM has partnered with LinKinVax to manufacture the protein subunit vaccine for the trial. The records I have for this vaccine are here – and you can see the slides of a presentation the developers made to the WHO in 2022 here. This month there were preclinical results for 2 pancoronavirus vaccines, both from China: There were results in mice for an intranasal vaccine from Sun Yat-Sen University. It is a mosaic nanoparticle vaccine – a method for carrying fragments from multiple different versions of coronaviruses. This one includes RBD fragments of 6 SARS-CoV-2 variants – the original, Delta, and 4 Omicron variants. Mice developed signs of immune response to more than 6 Covid variants, as well as original SARS. Results in mice for a protein subunit vaccine with an adjuvant, from Fudan University. The mice developed signs of immune response to SARS-CoV-2 variants, original SARS, and other coronaviruses, including MERS. This was the fourth set of results in my database from this group. Back to contents Addendum 1: Table of mucosal vaccines in clinical trials * Indicates new entry since my 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 2: Pancoronavirus vaccines with preclinical results * Indicates new entry since previous update post. Back to contents Addendum 3: 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. 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: 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 cartoons are my own (CC BY-NC-ND license). (More cartoons at Statistically Funny.) [END] --- [1] Url: https://absolutelymaybe.plos.org/2023/08/25/more-next-generation-covid-vaccines-are-heading-into-clinical-trials-update-10/ Published and (C) by PLOS One Content appears here under this condition or license: Creative Commons - Attribution BY 4.0. via Magical.Fish Gopher News Feeds: gopher://magical.fish/1/feeds/news/plosone/