A Bumper Month for Trial Results of NextGen Covid Vaccines (Update 23)

There is a lot to dig into in this monthly update! There are 7 new reports of data from clinical trials for next generation Covid vaccines. One shows another vaccine outperforming current mRNA vaccine: This time, it’s the GeoVax vaccine, in a small phase 2 trial for people with suppressed immune systems. There are also trials of mucosal vaccines measuring mucosal immune response. There are still no reports from studies that have tried to measure clinical effectiveness against Covid transmission, though.

In this update, there are 12 reports of preclinical research as well, across the different types of next generation vaccines. Plus, there’s news from the Coalition for Epidemic Preparedness Innovations (CEPI) on ways some drug regulatory agencies expect to handle pancoronavirus vaccines, and news on CEPI funding for mucosal vaccine development. There is some news, too, from the group developing human challenge trials for mucosal Covid vaccines in England.

There is good news from US Project NextGen, with a major milestone reached and another company awarded funding for a phase 1 trial. This post begins there, with a section on news from the US – including the ominous prospect of the US government swerving towards anti-vaxdom.

After that, I have the news from the last month broken down into 3 categories of next-generation Covid vaccines as usual (definitions below). Each section ends with an overview of vaccines in the category – and each has 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 the US
• 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 preclinical results
• Addendum 4: Definitions of vaccine types

News from the US

Potential impact of the US election

The recent election has kicked up a lot of uncertainty. We definitely need to prepare for vaccine misinformation issuing from government channels or spokespeople, and I’ll be posting soon about that. I think it’s hard to be sure about much beyond that at this stage. Even very recent predictions about the potential impact of the incoming administration aren’t aging well.

This article, for example, pointed out that the government “could slow production of existing vaccines or thwart the approval of new ones” – by demanding additional studies or delaying factory inspections, or affecting reimbursement. But there was also talk of guardrails and this quote: “The fringe people are unlikely to be in positions of real power.” That was about a week before someone accurately described in Wikipedia as “an anti-vaccine activist and conspiracy theorist” was nominated to spring to the top of the health power hierarchy, and similarly grim announcements followed quickly.

I think it’s hard to consider the implications of the new administration, though, when we don’t know what impact the pharmaceutical industry might have. This is a sector with seriously deep pockets for legal battles as well as lobbying. An analysis of the pharma and health product industry’s expenditure on lobbying and campaign contributions in the US from 1999 to 2018 estimated it was over a quarter of a billion dollars a year back then – including contributions for senior legislators. Months before the election, Politico reported that Pharma lobbying was already on the increase. Along with the potential for shocking developments, there’s a a possibility of long grinding battles.

For these updates, I’ll be keeping an eye out for developments that could affect progress or access to next generation Covid vaccines – for example, if manufacturers shift their priorities from the US to Europe or other parts of the world, or there’s an impact on Project NextGen.

Meanwhile, let’s look at recent good news from that program.

First phase 2B “mini-efficacy” trial underway and registered

As I reported last time, Vaxart’s trial for its oral vaccine has begun, aiming to recruit 400 participants as a sentinel cohort to closely assess safety. The trial is now registered – the first of the “mini-efficacy” trials. Vaxart have reported that they expect to have fully recruited the group by the end of November. If all goes well, they can go ahead and recruit the rest of the 10,000-participant trial, with half randomized to Vaxart vaccine, and half to either the Moderna or BNT/Pfizer vaccine.

Participants are being recruited at 145 locations around the US. If you are interested, you can see the locations by scrolling down the trial registration record to the “Contacts and Locations” section. There’s an email address and phone number there, too.

(All records for the Vaxart vaccine in my collection here.)

Second NextGen-funded pancoronavirus vaccine trial announced

PopVax, an Indian company, announced that they have received Project NextGen funding to run a phase 1 trial of their pancoronavirus mRNA vaccine in the US in early 2025. The company has previously received over US $1 million in funding from the Gates Foundation. As far as I know, there haven’t been any publications yet about this vaccine.

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Mucosal vaccine news

This section begins with vaccine development news, followed by a listing of recent results. That begins with 4 reports of clinical trials for mucosal vaccines. I added 6 preclinical study reports for mucosal vaccines this month, too: 4 of those are included in this section after the clinical trials. The other 2 preclinical reports are for mucosal vaccines included below in the “variant-proof” and pancoronavirus categories.

News from the human challenge studies project for mucosal vaccines, and from CEPI

There’s some news from the MUsICC Project, the international consortium for human challenge studies for mucosal Covid vaccines led by Imperial College London. (I discussed the background here.) The project leader, Christopher Chui, said in an interview that they are creating a dedicated facility for these studies in West London: “By being co-located in a hospital, the new space will allow more detailed study of those taking part in studies and how infections transmit between individuals.” There are interesting interviews with others involved in ICL’s human challenge studies, including studies in malaria and a network supporting low- and middle-income countries called HIC-Vac.

The international organization, CEPI, announced that it has funded Swedish company Abera to advance its mucosal OMV-based vaccine platform. It is not specifically for a Covid vaccine, but it’s part of their strategy to have the capacity to have what they call “plug and play” options for responding extremely quickly to a pandemic of a new infectious disease. Abera announced that the funding would be used for studies of their influenza vaccine. The company also has done preclinical work on a Covid vaccine. (I have a preclinical report for it in my collection.) This week, Abera received a European patent for their vaccine technology.

Clinical trial news for mucosal Covid vaccines

As discussed above, Vaxart’s phase 2b trial for their oral vaccine has recruited its first group of participants, and become the first Project NextGen-funded “mini-efficacy” to be registered.

There were 4 reports of clinical trial results this update. This includes 2 small trials which measure signs of nasal immunity in vaccines which have already been rolled out (phase 3 and phase 4), and I start with those below. That is followed by 2 phase 2 trials – one of which had previously been a preprint, and one that is a brief trial efficacy readout from the manufacturer.

Small phase 4 trial of Iran’s Razi Cov Pars intranasal vaccine booster tested mucosal immunity

Razi Cov Pars was the first mucosal vaccine rolled out, in Iran (in October 2021). It’s a protein subunit vaccine, with 2 injected doses followed by an intranasal dose. This trial randomized 193 previously vaccinated participants to a booster of Razi Cov Pars or adjuvant only placebo. Participants were followed up by weekly phone calls for a month. The rate of adverse reactions participants reported were low, and similar in both groups.

Blood and saliva samples as well as nasal swabs were collected before the intervention and 14 days afterwards. Collecting saliva samples was a challenge, and there were concerns about contamination affecting accuracy. The researchers detected no difference in signs of immune response in the blood and saliva samples between the groups after intervention. However, there were increases in Covid-specific immune responses in nasal secretions of the vaccinated group (IgA and IgG), and for one of those (IgG), the rate was significantly higher than for placebo.

(All records for this vaccine in my collection here.)

Small phase 3 trial of CanSino’s Convidecia aerosolized booster compared mucosal immunity with the BNT/Pfizer vaccine

Convidecia is a viral vector vaccine based on adenovirus 5 developed by CanSino in China. It has been rolled out in 3 countries, beginning in late 2022, and is administered by injection, or inhaled through a device similar to an asthma puffer.

There were 540 participants in this phase 3 trial in Malaysia, who had all previously had 3 doses of Covid vaccine. They were randomized to either an inhaled dose of Convidecia or an injected booster of the BNT/Pfizer mRNA vaccine. The people who had the inhaled vaccine reported a lower rate of adverse reactions (39% vs 65%).

The BNT/Pfizer vaccine took effect more quickly than Convidecia, so immune responses were initially higher. Immune responses after Convidecia peaked after 4 weeks, and by close to 6 months, antibodies were similar.

The researchers studied signs of mucosal immunity (SIgA) to multiple Covid variants in the saliva of a subset of 81 participants. Results were similar for some variants for both vaccines, and higher with Convidecia for some variants. Overall, though, the effect of both boosters was modest. (The trial register record for this trial is here.)

(All records for this vaccine in my collection here.)

Phase 2 trial testing intranasal vs injected booster of Patria vaccine or placebo in Mexico

This is a journal publication for a phase 2 trial of the Patria vaccine that I reported on earlier this year when a preprint was released. Patria is the version of the viral vector vaccine developed by the Icahn School of Medicine Mt Sinai (USA) developed by AviMex in Mexico, available in both injected and intranasal forms. (The US version of this vaccine is being developed as an intranasal vaccine by the Mt Sinai-spinoff, Castlevax: Project NextGen is funding a phase 2b “mini-efficacy” trial for it.)

There were 158 participants, and to be eligible, they had to have unusually low signs of existing immunity. The proportion of people with large increase in antibodies was higher for the injected version.

(All records for Patria specifically in my collection here.)

Press release on the phase 2a trial of Blue Lake Biotech/CyanVac‘s intranasal vaccine

This vaccine, called CVXGA, is a viral vector vaccine, based on PIV5 (parainfluenza 5). It was originally developed at the University of Georgia (USA), and this phase 2a trial was run in the US.

The version of CVXGA in the trial was based on an Omicron variant (XBB.1.5). There were 227 participants who had previously had Covid vaccination or Covid, and they were randomized to the vaccine or placebo. The results included in the press release were very positive, both for adverse reactions and the primary trial outcome measure for immune response. There was a secondary outcome measure of the signs of nasal immune response, but secondary results weren’t included in the press release. (The trial registry entry is here.)

This vaccine has Project NextGen funding for a phase 2b “mini-efficacy” trial, planned to start before the end of this year.

(All records in my collection for this vaccine here.)

New preclinical studies for mucosal vaccines

• Intranasal siRNA vaccine from the University of Lisbon (Portugal) and the University of Tel Aviv (Israel): This report describes tests of a protein subunit and siRNA (small interfering RNA) vaccine, including injections followed by intranasal boost in mice, including Covid challenge tests.
• Intranasal virus-like particle vaccine (VLP) from Mahidol University (Thailand): This reports tests of a VLP vaccine included intraperitoneal (into the lung) and intranasal administration in mice.
• Intranasal viral vector vaccine from Shanghai Jiao Tong University (China): This report includes testing of intranasal vaccine in both immunocompromised and healthy mice. The vector for this vaccine is VSV (vesicular stomatitis virus).
• Intranasal protein subunit vaccine from West China Hospital, Sichuan University (China): This report describes tests of vaccine injections followed by intranasal boost in mice, including Covid challenge testing.

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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; trial registration here); and
• Phase 2b for the intranasal viral vector vaccine from Blue Lake Biotech/CyanVac (planned to start in 2024, in US fall).

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Durable or “variant-proof” vaccine news

This update, I’ve added 3 more reports of clinical trials for vaccines in this category to my collection – from phase 1 to phase 3, as well as 4 reports of preclinical studies.

Phase 3 trial results of the self-amplifying mRNA vaccine from Arcturus Therapeutics (USA) versus the Oxford/AstraZeneca vaccine

This is LUNAR-COV19, the samRNA vaccine that was the first vaccine to demonstrate more durable Covid protection than the BNT/Pfizer vaccine. It has recently been rolled out in Japan (under the trade name Kostaive). The comparison in this latest report comes from the major efficacy trial for this vaccine. The trial was primarily placebo-controlled, and ran during Delta and Omicron waves in Vietnam. Within that trial, 2,366 people were randomized to a primarily safety and immunogenicity comparison of LUNAR-COV19 and the Oxford/AstraZeneca vaccine (ChAdOx1 nCov-19).

Adverse reactions for the vaccines were similar. Again, signs of immune response for the samRNA vaccine outlasted those of the comparison vaccine. Vaccine efficacy was also superior, though the size of this part of the study was too small for a precise estimate.

(All records in my collection for this vaccine here.)

Trial efficacy readout from GeoVax for the phase 2 trial of a 2 booster shots for people with chronic lymphocytic leukemia (CLL)

GEO-CM04S1 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 – and it is one of the vaccines being funded by Project NextGen for phase 2b “mini-efficacy” trial in healthy people in the US.

As I’ve written before, results for this vaccine for people with immunosuppression have been encouraging. That includes a company presentation reporting that results against variants have been durable for more than 12 months. Now the company has issued a press release after interim data review for their phase 2 trial for 80 people with CLL, comparing it with the standard mRNA boosters.

Their data safety board found that the mRNA did not meet the study’s primary endpoint – but GEO-CM04S1 did. That means that to this point, the GeoVax outperformed mRNA. The GeoVax vaccine includes both the Spike (S) and Nucleocapsid (N) antigens of the virus that causes Covid, whereas the mRNA vaccines include only the Spike. The board’s conclusion means the trial will continue to recruit people for the GeoVax vaccine only. (The trial is recruiting at the City of Hope Medical Center in California.)

(All records in my collection for this vaccine here.)

Results from another phase 1 trial 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. Last time, I reported on results from another phase 1 trial for this vaccine as a booster, run in Germany and the US. The developers had reported that the second dose did not appear to further boost immunity, and a higher dose than they tested might be needed. In this second phase 1a trial run of a Prime-2-CoV_Beta booster in Germany, they concluded again that the safety and immune response data were positive, but a higher dose was worth testing. (This trial had started just a few days after the first one.

(All records in my collection for this vaccine here.)

New preclinical reports of “variant-proof” vaccines

Oragenics (USA) is developing an intranasal protein subunit vaccine aiming to be “variant-proof” (called NT-CoV2-1). They also developed a test mRNA vaccine for the studies in their latest report. The developers based versions of the vaccine on the original SARS-CoV-2 strain and a range of variants. Then they tested for signs of immune response to a variety of sarbecoviruses in vaccinated mice. The developers concluded that vaccines based on Omicron apparently offer “drastically less” protection against sarbecoviruses, suggesting that the original Covid strain may be a more reliable basis for vaccines aiming for broad coronavirus protection.

The other 3 preclinical reports in this category:

• Researchers from the University of Pittsburgh (USA) reported on testing a vaccine based on proteins from SARS-CoV-2 and a DNA tumor virus (Kaposi sarcoma herpesvirus LANA) in mice.
• Researchers from Centro Nacional de Biotecnología, the Spanish National Center for Biotechnology, reported on 2 vaccines based DNA or MVA (Modified Vaccinia virus Ankara) vectors, also tested in mice.
• Researchers from Peking Union Medical College reported on tests of 3 protein subunit vaccines in mice, including SARS-CoV-2 challenge tests.

Skip ahead to next news category

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. Recently, minutes for a meeting at CEPI include notes of a discussion about the approaches drug regulators may take with these vaccines.

The regulators they consulted said they need a specific disease indication for a vaccine, not a disease group like “pan-sarbecovirus.” Data on additional disease coverage “would be welcome, but may not be included on the label.” According to those minutes, there was some variation among the regulators on the question of efficacy data, but all would require evidence to support each component in the vaccine. Vaccine candidates would need to show they perform at least as well as a SARS-CoV-2 vaccine already approved by that regulator.

Meanwhile, this field is still growing. This month, there is new data from a Phase 1 trial. Plus, I have added 4 preclinical reports to this category. In other news, another vaccine in this category has received Project NextGen funding as discussed above. However, there was bad news about one of the vaccines with clinical trial results: The manufacturers have declared bankruptcy (VBI Vaccines, Canada).

Phase 1 results from Gylden Pharma – formerly called Emergex (UK/USA)

This is a protein subunit vaccine, called Corona TcP. It focuses on T cell response, and is based on peptides (short proteins) with gold nanoparticle (GNP) adjuvant. The vaccine isn’t injected: It is delivered via a microneedle patch. The company aims to develop dry patches that don’t need refrigeration. Project NextGen is funding them to run a phase 1 trial, presumably in the US.

Last year, when this company was still called Emergex, they issued a press release about the results of their phase 1 trial in Switzerland, run during an Omicron wave. Now, there is a report of the results. As far as I know, there are no public reports of preclinical development of this vaccine. (The trial register entry this trial is here.)

The 26 participants in the phase 1 trial were randomized to groups of 10 for 2 doses of low- or high-dose vaccine, or groups of 3 for low- or high-dose adjuvant only. All but one participant had previously been vaccinated with at least 2 doses of other Covid vaccines.

All the participants reported adverse reactions, as the patch discolored the skin for about a day for almost everyone. There were 5 reports of severe (short-term) adverse reactions, and there were no serious adverse events. Immune response was difficult to interpret in this small group, with rates of previous vaccination and/or Covid so high.

New preclinical results

• Viral vector vaccine from Beth Israel Deaconess Medical Center (USA): This report is from 2022, but I had not previously tagged it to this category. It’s a viral vector vaccine (Rhesus Adenovirus 52), based on analysis of both types of SARS, and animal sarbecoviruses. It was tested in mice, with a Covid challenge test.
• Protein subunit vaccine from the China Cuba Joint Innovation Center (China, Cuba): This study tested 2 proteins designed as potential pancoronavirus vaccines in mice, via intranasal administration. (All records from this group in my collection here.) Antibodies in the mice cross-reacted with Omicron and the original SARS.
• Protein subunit vaccine from the University of Sydney (Australia): Tests in mice and hamsters of several versions of vaccine were reported here, including Covid challenge. The developers found that one of the candidates reduced clinical signs of disease in mice and hamsters. There were also signs of immune response to other sarbecoviruses in tests with mice that had been previously vaccinated with a current Covid vaccine.
• Viral vector vaccine from the University of Washington St Louis (USA): This is a trivalent mucosal vaccine based on proteins from 3 sarbecovirus clades (including both SARS), with an adenoviral vector. It was tested in mice with an injection followed by an intranasal dose. There were signs of immunity to all the sarbecoviruses they tested, but not to MERS. (Note: This group also developed ChAd-SARS-CoV-2-S, the vaccine used by Bharat Biotech to manufacture iNCOVACC, an intranasal vaccine rolled out in India.)

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/Ennodc (formerly LinkInVax) (France) – protein subunit.
  
  
• Osivax (France) – protein subunit (phase 1 trial fully recruited in June 2024).
  
  
• * VBI Vaccines (Canada) – eVLP. [This company announced bankruptcy in late 2024.]
  
  
• * 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.
• Unnamed (PopVax, India) – mRNA.

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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). * Results. 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. *539 people (Malaysia):Signs of serum immune response were lower for inhaled Convidecia than for injected BNT/Pfizer vax at 14 days, but grew for Convidecia to similar levels. Mucosal immune response (SIgA) was greater for Convidecia; the rate of adverse reactions was lower. 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. * Results (press release only).
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. (Previously available in preprint.)	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). * Results. 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.)	Phase 3: 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. * Phase 4: Immunogenicity and safety study of intranasal booster in 195 people, placebo-controlled. Increased IgA and IgG anti-RBD in nasal mucosa, but not in serum and saliva.
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
* Beth Israel Deaconess Medical Center USA RhAd52.CoV.Consv	Viral vector Sarbeco	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) * 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. (Formerly 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 Sydney Australia CoVEXS5	Protein subunit 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)	* This company declared bankruptcy in late 2024. 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
* Washington University in St Louis USA (Unnamed)	Viral vector Sarbeco	Non-primate (mucosal)
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 vaccines 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, with 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 and less so on BlueSky (hildabast.bsky.social).

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**** Note from PLOS: This blog was originally published on December 3, 2024. It did not properly port over when PLOS updated its blog platform, so it was reposted on December 20, 2024.

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 specifically on next generation Covid vaccines prior to this monthly series (beginning May 2023):

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)

All my posts on Covid vaccines, beginning from March 2020, are tagged here.

All previous Covid-19 posts at Absolutely Maybe

My posts at The Atlantic and at WIRED.

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 one working on vaccines. More about me.

The cartoon is my own (CC BY-NC-ND license). (More cartoons at Statistically Funny.)