(C) PLOS One This story was originally published by PLOS One and is unaltered. . . . . . . . . . . Mucosal Covid Vaccines Advancing, Plus a New Type of Vax in Development (Next Generation Update 16) [1] [] Date: 2024-04-30 This month, most of the news is in mucosal vaccine development again. These vaccines aim to block Covid infection. An aerosol vaccine from Canada is advancing into a mid-stage clinical trial. Plus, an intranasal protein subunit vaccine from Australia is going into a first-in-human clinical trial – the 28th mucosal vaccine to do so. There are some clinical results in this vaccine category, too. Plus, the recently announced international consortium for human challenge trials for mucosal vaccines has already had its first big meeting. In the “variant-proof” camp, there’s news of a major next generation development of a next generation vaccine! And I’ve added 13 preclinical studies to my collection – almost all for mucosal vaccines. As usual, I have the news broken down into 3 categories of next-generation Covid vaccines (definitions below). 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 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. 28 mucosal vaccines have reached clinical trial, although at least one of those has been discontinued. These 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. New this month: International human challenge consortium kick-off meeting: In my last update, I wrote about the new funding for this project to develop human challenge studies for mucosal Covid vaccines, called MusiCC, and led by Imperial College London. It’s supported with $57 million from the European Union and CEPI (Coalition for Epidemic Preparedness Innovations). They already had a 2-day meeting in London this month, with over 50 attending in person and another 30 or so online. Details of the discussion haven’t been published as yet. CEPI’s CEO spoke about the role of human challenge studies in achieving CEPI’s goal of a vaccine within 100 days of a new pandemic disease. The participants included the project’s Scientific Advisory Board – but I haven’t seen a list of the members. The lead investigator has been named: Professor Chris Chiu, from Imperial College London. All the consortium partners haven’t yet been announced either. The only ones I’ve seen mentioned were the oones I mentioned last time: Imperial College London, the University of Antwerp’s Vaccinopolos, and Singapore’s National Centre for Infectious Diseases. (This month I wrote about some of my thoughts on the ethics of this kind of study in my newsletter.) CanSino’s Convidecia (China) – more clinical trial results: This is an inhaled aerosol adenoviral vector vaccine that has been rolled out in several countries, beginning in China in September 2022. As far as I know, no study showing its effect on infection rates has been released. The latest publication of clinical trial results is for a phase 1/2 trial in 120 people, testing high, medium, and low doses, as well as varied forms (injections and/or inhaled). The highest immune responses came from the combination – an injection followed by an inhlaed dose. AeroVax (Canada) – inhaled vaccine is advancing to phase 2: This is an adenovirus-based vaccine developed by McMaster University, using several components of the SARS-CoV-2 virus. The goal is to develop a vaccine that is more durable and resistant to new variants, as well as providing mucosal immunity. Originally called ChAd-triCoV/Mac, the phase 2 trial will be run in Canada, for 350 people who have had at least 3 doses of an mRNA Covid vaccine. They will get a single aerosol dose of either the vaccine or a placebo via nebulizer – similar to the delivery system for inhaled asthma drugs. The start is planned for June. You can learn more about the background to this vaccine from the lead developer here, including a video. (Records in my collection for this vaccine are here.) Spikogen (Australia) – the latest mucosal vaccine to reach clinical trial: This one is a protein subunit vaccine which has been in use in Iran as an injection. It’s now going into a phase 1 trial for 100 people in Australia in oral/sublingual form. It’s a blinded crossover trial, with one group getting 2 oral doses of Covid vaccine and crossing over to 2 doses of an oral influenza vaccine. Another group will get the Covid and influenza vaccines combined, with crossover to an inactivated influenza vaccine as control. (My explainer on this type of trial is here.) (Records on this vaccine in mucosal form here.) New preclinical results: I’ve added 11 preclinical reports on results for mucosal vaccines to my collection since the last update, including one in the pancoronavirus category below. Other notable studies include: National Institute of Allergy and Infectious Diseases (NIH NIAID) (USA): This is the second report for a viral vector vaccine (based on murine pneumonia virus). After receiving 2 intranasal/intratracheal doses, 3 out of 4 macaques did not get infected in a SARS-CoV-2 challenge, while all the control animals did. (The first study report was also in macaques.) University of Guelph (Canada): This is the second report for a viral vector vaccine (based on Newcastle virus). The study involved intranasal/intratracheal vaccination of macaques. (The first was in hamsters.) The developers concluded that 2 mucosal doses of this vaccine provided “significant protection” against infection, based on a variety of swabs. Oragenics (Canada): This is the first report for an intranasal study of NT-CoV2-1, the protein subunit vaccine developed with Inspirevax and the National Research Council of Canada. Mice received the vaccines intramuscular version, then a group were given an intranasal boost, and all the mice were challenged with SARS-CoV-2. The developers concluded the boost enhanced protection. (Note: I had previously included this in the pancoronavirus table as a major review had included it in that category. However, this paper does not suggest a goal beyond SARS-CoV-2.) National University of Singapore: This paper reports on early experimentation with developing an intranasal mRNA vaccine. The vaccine was tested in mice, and included a lypholized (freeze-dried) version. Back to contents Durable or “variant-proof” vaccine news This month, I added only one preclinical study report for a vaccine from the Freie Universität Berlin. In this study in mice, the developers tested a version of the vaccine that merged genes from 4 Covid variants (alpha, beta, gamma, and delta) in an adenoviral vaccine. They detected signs of immune response to variants including Omicron. In other news, a developer of the Geovax vaccine told a conference that they expect to see phase 2 results this year. This is the vaccine being tested in people with cancer that I have reported on several times. (Records in my collection for this vax here.) Note: This is a rather vague category, including vaccines that aim to be more durable. I don’t include a table for tracking these vaccines. That’s because while I’m quite confident I’ve tagged all the vaccines in my collection that fall into the other 2 categories of next generation vaccines, 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); Gritstone Bio (self-amplifying mRNA). Neither of these trials has 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. This month there is news on technological developments for one vaccine, and a preclinical study report for another 2. VBI Vaccines (Canada) – development news: This vaccine has an ongoing phase 1 clinical trial. The company has announced that $28 million (Canadian) of their grant from the Canadian government will be directed towards developing a next generation of their enveloped virus-like particle vaccine (a type of protein subunit vaccine). They are calling this new platform MLE – for mRNA-launched enveloped. The aim is to reproduce eVLPs in the body. University of Wisconsin-Madison preclinical study report: This preclinical study is the fourth reported for this vaccine. The developers tested versions of the vaccine in mice, including challenge tests for SARS-CoV-2 and several sarbecoviruses. China Cuba Joint Innovation Center: This paper reports on a mucosal version of protein subunit vaccine using protein from the Delta variant. The mice showed signs of immune response to Omicron and the original SARS, but not to MERS and another coronavirus. 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: DIOSynVax (Cambridge University spin-off, UK) – mRNA. INSERM/LinkInVax (France) – protein subunit. Osivax (France) – protein subunit. 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 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 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: 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.) [END] --- [1] Url: https://absolutelymaybe.plos.org/2024/04/30/mucosal-covid-vaccines-advancing-plus-a-new-type-of-vax-in-development-next-generation-update-16/ 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/