Strong Longterm Results – and a NextGen Anti-Vax Campaign (Covid Vax Update 22)

There’s a lot of big news in next generation Covid vaccine development this month, including clinical trial results for 2 vaccines. The best and the worst news both relate to one of those vaccines – the self-amplifying mRNA vax developed by Arcturus. Their new phase 3 trial report marks the first time a vaccine has shown considerably more durability after a year than a first-generation mRNA vaccine.

Unfortunately, anti-vax campaigning is proving to be awfully durable, too. A wild theory about mRNA vax from the US swept into Japan, the first country to roll out the Arcturus vaccine, with devastating results. With anti-vax campaigners in America cheering all this on, it’s a painful reminder that the challenges for next generation Covid vaccines might not end even when they clear stringent drug regulators’ hurdles. (You can jump straight to that news here.)

Thankfully, there’s lots of encouraging news of scientific progress. For example, the international consortium to develop and run human challenge trials for mucosal Covid vaccines now has a website, listing its partners. Called the MusiCC Project and led from Imperial College London, it includes 20 research institutions from 6 countries, mostly from Europe and the US. (I wrote about the social aspects of this a few months ago.)

There’s also a bunch of good news from the US Project NextGen, including the first funding from that program for a pancoronavirus vaccine, a “mini-efficacy” trial off the starting blocks, and testing out smartwatches for real-time data collection in vaccine trials. I start with a section on that. And there’s more preclinical research – including another study showing prevention of transmission in co-housed lab animals. Plus, a complex vaccine gets a manufacturer, which might be the next clinical trial in the pancoronavirus category.

As usual, I have the news from the last month broken down into 3 categories of next-generation Covid vaccines (definitions below). Each section ends with an overview of vaccines in the category – and there’s a link to skip over that straight to the next news section.

ICYMI, check out my May post, “When will we get a sterilizing Covid vaccine?”

• News from US Project NextGen
• Mucosal vaccine 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

News from US Project NextGen

First phase 2B “mini-efficacy” trial kicking off

The first of the Project NextGen-funded phase 2b “mini-efficacy” trials apparently kicked off this month, although I haven’t yet found a trial register entry for it. Vaxart announced that the trial for their oral Covid vaccine would begin with a 400-participant sentinel cohort. Half will be randomized to the Vaxart vaccine, and half to either the Moderna or BNT/Pfizer vaccine.

Those 400 participants will be studied very closely to assess safety. Recruitment for the rest of the 10,000 would follow after an independent monitoring board and FDA give the all-clear. (The company’s first-in-human, safety phase 1 trial had 35 participants.) (All records for the Vaxart vaccine in my collection here.)

First NextGen-funded pancoronavirus vaccine announced

Gylden Pharma is a UK-based company, with a subsidiary in the US. It recently changed its name – previously, it was called Emergex. The company announced Project NextGen funding for an early phase trial for their protein subunit vaccine against betacoronaviruses, called CoronaTcP. This is presumably for a phase 1 trial in the US, but that’s not clear.

As far as I know, there haven’t been any publications yet about this vaccine. Last year, the company announced their phase 1 trial with 26 participants in Switzerland had positive results. They have also registered a phase 1/2 trial for the Philippines, which has not begun recruiting. (All records in my collection for this vaccine here.)

Trying out a smartwatch to collect vaccine trial data

This is part of Project NextGen, though it does not involve a new type of vaccine. It’s part of a phase 4 study with 4,000 people who have had currently available vaccines, called Project Remote. It’s a decentralized study that aims to collect data on correlates of protection among a more diverse group of participants than can participate in trials based at major hospitals.

The company running this trial announced that they will assess the feasibility of using a specific smartwatch to collect real-time continuous data “to potentially forecast COVID-19 infections.”

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Mucosal vaccine news

As discussed above, Vaxart announced that its Project NextGen-funded phase 2b “mini-efficacy” trial initiated a sentinel group. And I added 4 preclinical study reports for mucosal vaccines, one of which is discussed below in the variant-proof vaccine category. The other 3 reports include one which tested whether vaccination could prevent transmission from co-housed infected animals:

• Oral protein subunit vaccine from US Specialty Vaxform (USA): This report describes the formulation process for the vaccine, as well as tests in mice. The developers compared immune responses and thermostability of liquid and powder versions. (All records in my collection for this vaccine here.)
  
  
• Intranasal protein subunit vaccine from The Catholic University of America (USA): This vaccine targets both Covid and influenza. The developers report that 2 doses of the vaccine protected mice in challenge tests for each disease.

• Intranasal live attenuated virus vaccine from the University of Basel (Switzerland): This vaccine was tested in hamsters, using 2 versions of the vaccine. After challenge tests of both vaccinated and unvaccinated hamsters, the animals were co-housed. The developers report that the vaccine provided protection against transmission. One of the measures in the study was weight loss, as a symptom of disease impact. All the unvaccinated animals lost weight, but none of the vaccinated ones did. (This paper was preceded by a preprint.)

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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.
• 31 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:

• Phase 1 for MPV/S-2P, the intranasal viral vector vaccine developed by the NIH’s National Institute of Allergy and Infectious Diseases (NIAID). This trial for 60 participants began recruiting in July 2024.

• Phase 2b (“mini-efficacy”) for the intranasal protein subunit vaccine from Castlevax (planned to start in the last quarter of 2024);
  
  
• Phase 2b for the intranasal live attenuated vaccine from Codagenix;
  
  
• Phase 2b for the oral viral vector vaccine from Vaxart (trial start announced at the end of September 2024; no trial registration as yet); and

• Phase 2b for the intranasal viral vector vaccine from CyanVac (planned to start in 2024, in US fall).

Only the first of these trials (Phase 1) has been registered at ClinicalTrials.gov so far.

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Durable or “variant-proof” vaccine news

This update, I’ve added reports of results for 3 vaccines in this category to my collection, including results from 3 clinical trials as well as 2 preclinical studies. One of those vaccines is the subject of the anti-vax campaign I mentioned in this post’s intro, and I discuss that below too.

Phase 3 trial results for the self-amplifying mRNA vaccine from Arcturus Therapeutics (USA)

The self-amplifying mRNA vaccine from Arcturus Therapeutics, called LUNAR-COV19, is the first next-generation Covid vaccine authorized in a country with a WHO-designated stringent drug regulator – Japan. It’s marketed there under the trade name, Kostaive.

Late last year I provided a short overview of the clinical trials for this vaccine, including 4 early-to-mid phase trials in Singapore and the US, a phase 1 to 3 trial in Vietnam with over 16,000 participants in phase 3, and a small phase 3 trial in Japan with 828 participants where the vaccine went head-to-head with BNT/Pfizer’s mRNA vaccine on immunogenicity and adverse reaction parameters. In April, I summarized the 3-to-6-month follow-up for that trial – showing the vaccine was outperforming BNT/Pfizer’s vaccine, with substantially less waning of immune response.

This month, 12-month follow-up data for that trial were published, as well as results of another immunogenicity-based phase 3 trial, head to head with Omicron-adapted versions of the Arcturus and BNT/Pfizer vaccines, in Japan.

First the 12-month follow-up. In that trial, participants had previously had at least 3 doses of a first-generation mRNA vaccine. They were randomized to a booster of either LUNAR-COV19 (5 μg) or the BNT/Pfizer vaccine (30 μg). Signs of immune response to the original SARS-CoV-2 and Omicron BA.4-5 were measured. At 1 month, immune response was similar between the 2 groups for the original Covid strain, but the Arcturus vaccine performed better against Omicron.

At 3-6 months, the authors only published results for people who had had no signs of Covid infection. There was substantially less waning of immune response for LUNAR-COV19 than for BNT/Pfizer, though there was still some.

The new 12-month data now includes data for all the participants, at each time point. In addition, there are data for signs of immune response to Delta and additional Omicron strains. For all strains, the rate of immune response for the Arcturus vaccine remained substantially higher than for the BNT/Pfizer vaccine, though it had waned a little between 6 and 12 months.

The new phase 3 trial tested bivalent versions of the Arcturus and BNT/Pfizer vaccines, each including adapted versions for the Omicron BA.4/5 variant. Again, the participants had been previously vaccinated with at least 3 doses of a first-generation mRNA vaccine: 930 participants were enrolled. Again, the dose of the Arcturus vaccine was much lower than the dose of BNT/Pfizer vaccine. This report provides data at 1 month.

The authors report that vaccine reactions were similar between the 2 groups. They had immunogenicity data at baseline and 29 days for 398 participants in the Arcturus group and 405 in the BNT/Pfizer group. Signs of immune response to Omicron BA.4/5 were higher for the Arcturus group. Signs of immune response to Omicron XBB.1.5 were also higher for the Arcturus vaccine, though it was lower than for BA.4/5.

Anti-mRNA vax campaigning hits the Arcturus vaccine

The Arcturus vaccine is a self-amplifying messenger RNA (samRNA). That means it doesn’t just leave a message and disappear, the way current mRNA vaccines do. It makes copies of itself inside our cells – similar to the way a virus works. One of the advantages of samRNA is that much smaller doses of mRNA are needed. Self-amplification theoretically extends the durability of the vaccine, and the trials of the Arcturus vaccine shows that it can do this.

Fearmongering about the vaccine in Japan has been so successful, that there are businesses saying people who have been vaccinated with it are not allowed in their premises. The claim frightening people is that “the vaccine will make an infinite number of proteins in the body or its components will be transmitted to others.”

I’m not sure where this far-fetched theory began. A major influence has been the Japan Nursing Ethics Association. In August, they released a statement expressing concern about the safety and ethics of introducing this vaccine, and it’s an extraordinary document to come from a professional association. It uses hot button language (like genetic engineering) and a kind of conspiracist pseudoscience.

Their first argument is that there’s something suspicious about the vaccine only being available in Japan, and it shouldn’t be trusted as a result. They also say it’s the first samRNA vaccine to be authorized in the world. That isn’t true, but that has been part of the marketing of the Arcturus vaccine.

The Arcturus vaccine is actually the second self-amplifying mRNA vaccine that’s been authorized internationally. Both vaccines were licensed by the developers to local manufacturers for authorization in their countries. The first, Gemcovac, was authorized in India in 2022. The Arcturus vaccine, LUNAR-COV19, was authorized late last year in Japan, and rolled out recently, under the trade name Kostaive. It’s made and marketed in Japan by Meiji Seika Pharma, which also ran the studies in Japan.

I don’t think Japan being first to market is sinister. It’s gotten truly bizarre though. I won’t link to the US anti-vax websites that are promoting this idea, but they’re throwing around language like “third atomic bomb” and humanity being destroyed.

As I’ve reported in a previous post, Arcturus has also filed an application for authorization of this vaccine in Europe. They have a licensing partnership with Australia’s global biotech, CSL Seqirus. CSL Seqirus reports that they are seeking authorizations, but not in which countries. They have a new facility in Boston which will manufacture the vaccine. CSL Seqirus is also building an mRNA facility in Melbourne, though that won’t be operational soon. Arcturus reported that there had been discussions on the design of its phase 3 booster trial with the US FDA and the regulatory authorities for Europe and the UK.

There’s no scientific basis either, for the Nursing Ethics Association’s claims that the vaccine could be dangerous, with vaccinated people somehow transmitting samRNA to other people, and of course, professional societies with vaccine expertise have spoken up against it. The Nursing Ethics Association statement cites an article to support their argument. It’s an opinion piece from 2021 about “some possible unintended consequences” of mRNA vaccines, written by a naturopath from the US and someone from the Computer Science and Artificial Intelligence Laboratory at MIT.

Their theory? It’s based on the possibility of short-term viral shedding after administration of some live vaccines. But mRNA vaccines aren’t based on live virus, as has been stressed by so many since these claims first started. See here from the US CDC, for example. The Wikipedia page on this calls it “a popular anti-vaccination myth.” The Nursing Ethics Association also claims that whether or not mRNA can alter human DNA is an open question. However, mRNA doesn’t enter cells at all – it just passes on a message. (See the US CDC again: “COVID-19 vaccines do not change or interact with your DNA in any way.”)

The samRNA anti-vax campaigning is a bit like the mRNA one on steroids. As samRNA vaccines become more widely available, explaining why mRNA that replicates isn’t a risky proposition is going to take a lot of work. I’m thinking of writing more about this, so if you have any good studies or examples of good debunking, I would appreciate hearing about them.

Phase 1 trial results, plus a preclinical study report, for Prime-2-CoV_Beta, a viral vector vaccine from Speransa Therapeutics and the University of Tübingen (Germany)

The viral vector for this vaccine is orf, a type of poxvirus. The phase 1 trial for the vaccine included 72 participants, in Germany and the US. All but 12 of the participants had been vaccinated previously with at least 2 doses of either the Moderna or BNT/Pfizer mRNA vaccine, and received 2 doses of Prime-2-CoV_Beta, 4 weeks apart. The trial tested 4 dosage levels of the vaccine in a group aged 18-55, followed by a dose confirmation test in participants aged between 65 and 85.

Participants had typical vaccine adverse reactions after each shot, with severe reactions in 3 people. There were also 4 severe or serious adverse advents that were not judged vaccine-related. The developers concluded a higher dose was needed to achieve signs of immune response, which was shown for a range of variants, though weaker for Omicron. They did not find development of antibodies to the viral vector after 2 doses. The developers reported that the second dose did not appear to further boost immunity, and a higher dose than they tested might be needed.

The developers also published a report of preclinical studies of 2 versions of this vaccine in mice and hamsters, and 1 version in macaques, including mucosal administration. The developers report on challenge tests of several Covid variants, including Delta. In primates, the vaccine protected the virus from reaching the lungs of 80% of the primates at 5 months, while the virus reached the lungs of all those in the control group.

Preclinical study report for a protein subunit vaccine from National Taiwan University (Taiwan)

This group of scientists had developed a monoclonal antibody for all Covid strains. In this new report, they used it as a basis for an experimental vaccine. After testing it in mice and finding signs of immune response to a range of variants, the authors concluded that it could be developed into an effective variant-proof vaccine.

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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, and an October rollout is planned, with the trade name, Kostaive.

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.

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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, I have added 2 more vaccines to my collection, including the one receiving Project NextGen funding as discussed above. This brings the number of pancoronavirus vaccines reaching clinical trials to 6.

The second vaccine I added this month was developed at Stanford University (USA). It is a protein subunit vaccine incorporating components of 4 strains of coronavirus – SARS, the original SARS-CoV-2, Omicron BA.4/BA.5, and MERS. The developers released a report of preclinical studies in mice, showing signs of immune response to all 4 strains.

In other news, there’s been an important development with the California Institute of Technology (Caltech) Mosaic-8b vaccine. Early last year I wrote about the hitch this group faced. The vaccine includes components from 8 coronaviruses, including SARS-CoV-2. They had reported could not go into clinical trial because with so many components, it was difficult to manufacture enough of the vaccine for a clinical trial.

This month, it was announced that Caltech has partnered with manufacturing groups from the UK, Ingenza and the Centre for Process Innovation, as well as the University of Oxford. A company spokesperson for Ingenza said they aim to develop a vaccine “rapidly,” using their platform “to reduce development time and costs, while establishing a scalable manufacturing process.” 

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 6 of these vaccines in phase 1 clinical trials, with some results for 3 of them marked *:

• * CoronaTcP (Gylden Pharma, UK/US) – protein subunit. (Note: This vaccine was previously called PepGNP-SARSCov2, and the manufacturer was previously called Emergex.)

• 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.

US Project NextGen-funded trials in this category:

• CoronaTcP (Gylden Pharma, UK/US) – protein subunit.

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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).

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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.

Vaccine, type, manufacturer	Mucosal version(s)	Phase 1 to 2 clinical trials	Phase 3+ trial(s)	Phase 3+ efficacy or immunogenicity results
ACM-001 Protein subunit ACM Biolabs (Singapore/Switzerland) (All records)	Intranasal.	Phase 1. Results (press release only)
Ad5-nCoV (Convidecia Air) Viral vector (adenovirus) CanSino (China) (All records)	Inhaled through the mouth using a nebulizer.	Phase 1. Results. Phase 1/2. Results (plus second later preprint). Phase 1/2. Results. Phase 2 (aged 6-17 years). Booster adapted for variant.	10,420 people in China (Phase 3). Results. 1,350 people (Phase 3). 540 people, in Malaysia (Phase 3). 904 people in China (Phase 4). Results. 360 people (Phase 4). 451 people (Phase 4). Results. 10,000 people in China (Phase 4). Results for a 4,089 in the Ad5-nCoV arms.	904 people: Comparison after 2-dose course of inactivated vax: Convidecia injection vs inhaled, protein subunit, or CoronaVac booster (Phase 4 results). Both injected & inhaled Convidecia had stronger impact on signs of immunity than the others; response after inhaled version was slower but longer-lasting than injected (which peaked then declined from day 14), better for Omicron though not as good for original virus. No measure of mucosal immunity used. 451 people: Comparison of different versions adapted for variant, including a bivalent version. Booster of inhaled Convidecia after previous vaccination with inactivated vaccine. Signs of immune response to Omicron were higher for the bivalent vaccine, though lower for the original SARS-CoV-2 strain. 4,089 people, plus a 2,008 un-randomized unboosted control group: This trial tested the original vax during Omicron, with either an injected or inhaled booster. There wasn’t a significant difference between them, though the injected version fell below their ineffectiveness threshold and the inhaled one reached effectiveness despite having a smaller dose of vaccine.
Ad5-S Viral vector (adenovirus) State Key Laboratory for Infectious Disease/Guangzhou Enbao Biomedical Technology Co (China) (All records)	Intranasal.	Infection prevention study.
AdCOVID Viral vector (adenovirus) AltImmune (USA) (All records)	Intranasal.	Phase 1. Results – press release only. Discontinued after phase 1.
AdS+N Viral vector (adenovirus) ImmunityBio (USA) (All records)	Intranasal, oral capsule, or sublingual.	Phase 1 (oral). Phase 1 (sublingual).
AeroVax (Ad5-triCoV) Viral vector (adenovirus) McMaster University/Canadian Institutes of Health Research (Canada) (All records)	Aerosol.	Phase 1 (& ChAd-triCoV/Mac). Phase 2.
Avacc 10 Protein subunit Intravacc (Netherlands) (All records)	Intranasal.	Phase 1. Results (press release only)
bacTRL-Spike-1 Live attenuated Symvivo (Canada) (All records)	Oral.	Phase 1.
BBV154 (iNCOVACC) Viral vector (adenovirus) Bharat Biotech (India) (All records) This vaccine is ChAd-SARS-CoV-2-S Washington University in St Louis (USA) (All records)	Intranasal.	Phase 1. Phase 2. Small amount of data from these trials in the drug product information. Phase 2/3. Phase 2.	In India, 2-dose course of BBV154 vs 2-dose course of injected Covaxin inactivated vaccine (Phase 3 – and here). Results (previously in preprint). See also the drug product information. 875 people in India, booster trial (Phase 3).	2,971 previously unvaxed people were assigned for the intranasal iNCOVACC, 161 for injected Covaxin. This trial did not aim to assess disease outcomes. It took place during the first Omicron wave. Signs of immune response were higher for iNCOVACC than Covaxin. Adverse events rate very low (5% local and 3% systemic) – lower than for comparison group.
B/​HPIV3/​S-6P Viral vector (parainfluenza) NIH’s National Institute of Allergy and Infectious Diseases (NIAID) (USA) (All records)	Intranasal.	Phase 1. Fully recruited by early July 2024.
BV-AdCoV-1 Viral vector (adenovirus) Wuhan BravoVax (China) (All records)	Inhaled through the mouth using a nebulizer.	Phase 1.
ChAdOx1 Viral vector (adenovirus) Oxford University (UK) (This is the AstraZeneca vax) (All records)	Intranasal.	Phase 1. Phase 1. Results.
CoV2-OGEN1 Protein subunit US Specialty Formulations/VaxForm (USA) (All records)	Oral.	Phase 1. (Fully recruited, final dose in November 2022.) Press release stating successful (without data) and progressing to phase 2 trial.
COVI-VAC Live attenuated Codagenix (USA, with the Serum Institute of India) (All records)	Intranasal.	Phase 1. Press release in 2021 stating successful (without data) and progressing to phase 2/3. Preliminary results (conference abstract in 2021) and in a 2022 press release. Results in 2023 (press release only). Phase 1 (booster).	Phase 2/3, as part of the WHO Solidarity Trial for Vaccines in Mali, Colombia, Kenya, Philippines, Sierra Leone. Fully recruited by July 2024. (Protocol.)
CVXGA1-001 Viral vector (parainfluenza) CyanVac/Blue Lake Tech (USA) (All records)	Intranasal.	Phase 1. Results (press release only). Phase 2.
DNS1-RBD (Pneucolin) Viral vector (influenza) Beijing Wantai BioPharm (China) (All records)	Intranasal.	Phase 1. Phase 2. Joint results.	30,990 participants in Colombia, Philippines, South Africa, Vietnam. Results (previously in preprint.) 5,400 participants in Ghana (Phase 3).	Comparison of 2 doses of intranasal vaccine 14 days apart, with placebo control, during circulation of Omicron. Included >13,000 previously unvaccinated people. Efficacy shown 90 days after 2nd dose. There was some decline at 180 days. Efficacy against symptomatic Covid: No previous vax: 55.2% (CI 13.8 to 76.7) Inactivated: 38.2% (CI -49.2 to 74.4) Viral vector: 39.9% (CI -16.7 to 69.1) mRNA: 10.1% (CI -45.9 to 44.5) Efficacy against severe Covid: No previous vax: 66.7% (CI 8.3 to 87.9) Inactivated: 54.6% (CI -47.3 to 86.0) Viral vector: 50.0% (CI -6.8 to 76.6) mRNA: 19.5% (CI -39.2 to 53.4) Efficacy against hospitalization: 100% (CI -9.2 to 100) Adverse events were very low – similar to placebo. Less than 8% of people had a runny and/or blocked nose or sore throat.
GAM-COVID-VAC (rAd26-S – Sputnik Light) Viral vector (adenovirus) Gamaleya Research Institute (Russia)	Intranasal.	Phase 1/2	7,000 participants in Russia (Phase 3 or phase 2/3 – not clear).
Mambisa Protein subunit Centre for Genetic Engineering & Biotechnology (CIGB) (Cuba) (All records)	Intranasal drops.	Phase 1/2. Phase 1/2. Results. Phase 2.
MPV/S-2P Viral vector (murine pneumonia) National Institute of Allergy and Infectious Diseases (NIAID) (USA) (All records)	Intranasal drops.	Phase 1.
MV-014-212 Viral vector (RSV) Meissa Vaccines (USA) (All records)	Intranasal drops or spray.	Phase 1. Results (press release).		This vaccine is in limbo because of the company’s financial difficulties.
MVA-SARS-2ST Viral vector (MVA) German Centre for Infection Research (DZIF)/IDT Biologika (All records)	Inhalation.	Phase 1.
NB2155 Viral vector (Adenovirus 5) Guangzhou Medical University/ Guangzhou National Laboratory (All records)	Intranasal.	Phase 1.
CVAX-01 Viral vector (Newcastle Disease Virus) Castlevax/Icahn Mt Sinai (All records)	Intranasal.	Phase 1. Results (press release).
Ad5-S-Omicron BA.1 Viral vector (Adenovirus 5) Guangzhou Medical University/Guangzhou National Laboratory (China) (All records)	Intranasal	Phase 1. Results.
Patria (NDV-HXP-S/AVX-COVID-12-HEXAPRO) Viral vector (Newcastle Disease Virus) Laboratorio Avi-Mex (Mexico) (All records on Patria, see also CVAX-01 for early development.)	Intranasal.	Phase 1. Results. Phase 2. Results.	Phase 2/3 for injected version only: Results.
PRAK-03202 Protein subunit Oravax (USA) [Oravax was established by OraMed (Israel) to develop this vaccine, using Premas Biotech’s PRAK-03202 and their oral vaccine technology] (All records on oral PRAK-03202, and on intramuscular version)	Oral.	Phase 1 (in South Africa). Results (press release only).
Razi-Cov Pars Protein subunit Razi Vaccine & Serum Research Institute (Iran) (All records)	Intranasal (third dose after 2 injections).	Phase 1. Results. Phase 2. Results. Phase 1 to 2 (in 12-17 year-olds). Phase 4 (Booster). Phase 1 to 2 (in 5-17 year-olds).	41,128 people in Iran, comparing the 3-dose course to 2-dose inactivated Sinopharm Beijing vax, only partially randomized (Phase 3). Results (Previous media report for the first 24,000 participants.)	The authors concluded Razi-Cov Pars was non-inferior to the inactivated vaccine, with similarly very low adverse events. However, the trial could not establish whether there was an advantage to an intranasal dose.
SC-Ad6-1 Viral vector (adenovirus) Moat Bio/Tetherex (USA) (All records)	Intranasal and inhaled.	Phase 1. Trial expanded to add an inhaled version (from 130 to 190 people). Results so far briefly mentioned in press release.
SpikoGen Protein subunit Vaxine (Australia) (All records on mucosal and on all forms.)	Oral/sublingual.	Phase 1.
(Unnamed) Inactivated bacteria DreamTec (Hong Kong) (All records)	Oral.	Phase 1. Phase 1. Phase 1. Note: An article of preclinical results has been retracted over lack of ethics committee approval.
VXA-CoV2-1/VXA-CoV2-1.1-S Viral vector (adenovirus) Vaxart (USA) (All records)	Tablets.	Phase 1. Results. Phase 2. (Started October 1, 2021.) Results (press release). Additional brief results in presentation. * Phase 2b. (Start announced September 30, 2024.)

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Addendum 3: Pancoronavirus vaccines with preclinical results

* Indicates new entry since previous update post.

Developer Country Vaccine name	Type of: Vaccine Coronavirus	Preclinical results	Clinical trial status
Academia Sinica Taiwan (Taiwan) (Unnamed)	mRNA All	Non-primate
Baylor College of Medicine (USA) (Unnamed)	Protein subunit Beta	Non-primate
Beijing University of Chemical Technology (China) (Unnamed)	Live attenuated pangolin coronavirus All	Non-primate
California Institute of Technology (Caltech) USA Mosaic-8b	Protein subunit Beta	Non-primate Non-primate Non-primate Primate, non-primate Primate, non-primate (update) (previous version) Non-primate (new version of the vaccine) Primate and non-primate
Charité Universitätsmedizin Berlin Germany NILV-PanCoVac	Viral vector All	Non-primate (mucosal)
China Cuba Joint Innovation Center China, Cuba Unnamed	Protein subunit Sarbeco	Non-primate (mucosal)
Codiak USA exoVACC Pan Beta Coronavirus	Protein subunit Beta	Article on development Non-primate (conference slides) Non-primate (conference slides)	(This company began proceedings in bankruptcy court. See news.)
DIOSynvax UK DIOS-CoVax/ pEVAC-PS	mRNA Sarbeco	Non-primate Non-primate Non-primate (a different vaccine)	Phase 1 trial (incl. protocol) (Up to 36 participants in the UK) Began December 2021. Fully recruited. Expanded to another city – no trial register entry found.
Duke University USA RBD–scNP	Protein subunit Beta	Primate Primate Primate, non-primate Non-primate (previously in preprint) Primate, non-primate
Francis Crick Institute UK (Unnamed)	Protein subunit with DNA boost All	Non-primate
Fudan University China HR1LS	Protein subunit Sarbeco	Primate, non-primate Primate Primate Non-primate
Georgia State University, University of Iowa USA SARS2-S (SARS-RBD)	mRNA Sarbeco	Non-primate Non-primate
Georgia State University USA Om-S-MERS-RBD	Protein subunit All	Non-primate
Georgia State University USA (Unnamed)	Protein subunit Sarbeco	Non-primate Primate, non-primate Non-primate
Guangdong Pharmaceutical University China (Unnamed)	Protein subunit All	Non-primate
* Gylden Pharma UK/USA CoronaTcP	Protein subunit Beta		Phase 1 trial (26 participants in Switzerland) Results (press release only) Phase 1/2 trial (Up to 110 participants in the Philippines) (Not yet recruiting)
Korea Research Institute of Bioscience and Biotechnology South Korea (Unnamed)	Protein subunit Sarbeco	Non-primate
INSERM Vaccine Research Institute/LinKinVax France PanCov (CD40.CoV2/RBDv)	Protein subunit Sarbeco	Non-primate Primate, non-primate Primate Non-primate (conference poster)	Phase 1/2 trial (Up to 240 participants in France) Booster trial, planned to start recruiting in February 2024.
Osivax France OVX033	Protein subunit Sarbeco	Non-primate	Phase 1 trial (48 participants in France) First participant vaccinated in February 2024. Fully recruited in June 2024.
Oxford University UK ChAdOx1.COVconsv12	Viral vector Sarbeco	Non-primate
Pennsylvania State University USA (Unnamed)	Protein subunit All	Non-primate
Scripps Research Institute USA (Unnamed)	Protein subunit Beta	Non-primate
SK Bioscience/ Uni of Washington/Uni of North Carolina at Chapel Hill South Korea, USA GBP511	Protein subunit Sarbeco	Primate, non-primate (testing Covid vaccine GBP510 against other sarbecoviruses)	More on plans for adapting this vaccine – GBP510 authorized as SKYCovione. See the University of Washington research listed below in this table.
Stanford University USA DCFHP-alum	Protein subunit Sarbeco	Primate Erratum (correction to legend in a figure). Non-primate
* Stanford University USA Unnamed	Protein subunit All	Non-primate
State Key Laboratory of Respiratory Disease Guangzhou Medical University China (Unnamed)	Protein subunit Sarbeco	Primate and non-primate
Sun Yat-Sen University China (Unnamed)	Protein subunit Sarbeco	Non-primate
University of Amsterdam Netherlands (Unnamed)	Virus-like particle Sarbeco	Non-primate
University of California Irvine/Techimmune USA (Unnamed)	Viral vector Beta	Non-primate (previously in preprint) Non-primate (mucosal) (previously in preprint) Non-primate (There was also a paper about this vaccine’s development in 2021.)
University of Houston/Auravax USA NanoSTING-NS	Protein subunit (intranasal) Sarbeco	Non-primate Non-primate Non-primate Primate, non-primate
University of North Carolina at Chapel Hill USA (Unnamed)	Viral vector Sarbeco	Non-primate (Previously in preprint)
University of North Carolina at Chapel Hill USA (Unnamed)	mRNA Sarbeco	Non-primate
University of Toronto Canada (Unnamed)	Protein subunit Sarbeco	Non-primate
University of Washington USA (Unnamed)	Protein subunit Sarbeco	Non-primate (Previously in preprint) Non-primate Non-primate (MERS vaccine developed on the same platform as GBP511.)	(See “GBP511” above in this table.)
University of Wisconsin-Madison (PanCorVac) USA (Unnamed)	Protein subunit All	Non-primate Non-primate Non-primate Non-primate
VBI Vaccines Canada VBI-2901	eVLP All	Non-primate Non-primate (Press release)	Phase 1 trial (103 participants in Canada) Began October 2022. Fully recruited. (Further background info.) Results (press release only). (101 participants) Previously vaccinated people boosted with 2 low or high doses, or 1 high-dose. Limited data reported. Some signs of immune response to a range of coronaviruses, mostly lasting at least 5 months. No major safety concerns.
Walter Reed Army Institute of Research (WRAIR) USA SpFN/ALFQ	Protein subunit Beta	Non-primate Non-primate Non-primate (incl RFN) Non-primate Primate Primate Primate (with J&J vax)	Phase 1 trial (US) Began April 2021, with 29 participants, including some on placebo. Results. Vaxed participants showed immune responses to several Covid variants and several sarbecoviruses, but no signs of response to MERS.
Walter Reed Army Institute of Research (WRAIR) USA RFN	Protein subunit Beta	Non-primate (incl SpFN) Primate
Yale University USA (Unnamed)	mRNA All	Non-primate Non-primate
Yale University/Xanadu Bio USA (Unnamed)	Protein subunit, intranasal booster Sarbeco	Non-primate

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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).

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You can keep up with my work at my newsletter, Living With Evidence. And I’m active on Mastodon: @hildabast@mastodon.online 

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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:

1. Mucosal vaccines (March 2022)
2. Pan-SARS-Cov-2 and pancoronavirus (July 2022)
3. Mucosal vaccines (July 2022)
4. Mucosal vaccines (September 2022)
5. Mucosal vaccines (April 2023)
6. Pancoronavirus vaccines (April 2023)
7. Next generation (May 2023)
8. Next generation (June 2023)
9. Next generation (July 2023)
10. Next generation (August 2023)
11. Next generation (September 2023)
12. Next generation (November 2023)
13. Next generation (January 2024)
14. Next generation (February 2024)
15. Next generation (March 2024)
16. Next generation (April 2024)

17. Next generation (May 2024)

18. Next generation (June 2024)

19. Next generation (July 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 began as a person worried about the virus, as my son was 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.)