Intranasal Vaccine Trial Results and More on Preventing Covid Infection (NextGen Vax Update 29)

This month, there are the first clinical trial results from an intranasal DNA vaccine, with some signs that it might protect against infection. The total number of mucosal Covid vaccines that have reached clinical trial is now 34. And a seventh pancoronavirus vaccine has reached clinical trial, too.

There is also a preclinical study that extensively studies the molecular action of intranasal Covid vaccines. In other news, the UK might be the next country to get access to a next generation Covid vaccine, with Arcturus planning to lodge an application for their self-amplifying mRNA vaccine there this quarter.

In the US, dosing has re-started in the first Project NextGen-funded “mini-efficacy” trial, but a major chunk of Project NextGen funding has been re-directed. I start with that news. 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:

• An introduction to self-amplifying mRNA, plus my compendium on getting ready for more mRNA fear-mongering.

• Check out my May 2024 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 preclinical results
• Addendum 4: Definitions of vaccine types

News from US Project NextGen

Let’s start with the bit of good news: Vaxart’s oral vaccine. It dodged the axe at Project NextGen. This week, the company announced that dosing for the 10,000-participant trial had begun. There are 145 locations for this trial around the US. If you’re interested in participating, contact details are here.

Some other grants have been cancelled, but I haven’t seen reports yet for several Project NextGen-funded clinical trials. All the originally-funded trials are listed at the end of each of category below, with their fate noted if it’s been reported.

This month began, though, with a swerve in direction for this funding – up to half a billion dollars diverted from Project NextGen to a project to develop inactivated universal vaccines, starting with influenza. It’s based on BPL-inactivation of a cocktail of influenza viruses – which is the type of inactivation used for the Covid vaccines from Sinovac (Coronavac) and Sinopharm in China. Those vaccines saved a lot of lives, but they were outperformed by the effectiveness of mRNA, protein subunit, and viral vector vaccines. That this project is being called “Generation Gold Standard” is bizarre. It’s not gold standard science, that’s for sure: It’s what Katherine Wu described in The Atlantic as “The NIH’s New Cronyism.”

There’s an excellent article by Jon Cohen in Science magazine digging into this. This didn’t emerge from any normal competitive scientific assessment process, but from a pitch by the developers to the Health Secretary (Kennedy). The Secretary just believes that vaccines based on components of viruses are inferior, and that’s that. Vaccine expert Stanley Plotkin is quoted by Cohen as calling this decision “appalling.” When he saw the announcement, Plotkin says, “I thought, ‘Have I missed something in the literature?’…Well, no, I haven’t.”

The announcement said they are aiming for inactivated universal influenza vaccine to reach FDA approval by 2029, and even if a Covid version really does follow, that would obviously be well down the track.

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Mucosal vaccine news

This month, I’ve added the results of a clinical trial for a vaccine I had not previously listed – bringing the total number of mucosal vaccines that have reached clinical trial to 34. The new trial report also includes results of preclinical experiments. I’ve also added another 8 preclinical reports for mucosal vaccines. One of these studies involved a new type of analysis of the impact of intranasal Covid vaccination on cells, and I’ve listed that study from Japan separately in this section. Another 2 are included in the pancoronavirus section below.

In other news, as discussed above, the Project NextGen-funded “mini-efficacy” 10,000-participant trial for Vaxart’s oral vaccine started dosing. And if you’re in Canada and looking for a trial to join, the AeroVax inhaled vaccine trial from McMaster University is still recruiting, and now has a trial website.

Phase 1 trial results for an intranasal spray of DNA vaccine after an intradermal dose from GeneOne Life Science (South Korea)

This is the first next-generation DNA vaccine against Covid with results. Like mRNA vaccines, these vaccines uses genetic components of antigens to induce immunity – but it’s DNA, not messenger RNA. (You can read more about DNA vaccines here.)

GeneOne Life Science’s vaccine is called GLS-5310, and the company received government funding to support its development. A previous phase 1 trial for this vaccine tested an intradermal booster (under the skin) using a suction device, with 48-week follow-up results. The theory behind using a suction cupping device after injection is to help the DNA disperse.

This new trial report has results comparing an intradermal booster alone, with an intradermal booster followed by a dose via intranasal spray. The report includes preclinical results of testing intranasal vaccine in rabbits.

The phase 1 trial was run in the US and Puerto Rico during Omicron, and the version of the vaccine was not adapted for Omicron. There were 70 participants who had previously been vaccinated with BNT/Pfizer, Moderna, or J&J Covid vaccine. Participants were randomized to 4 groups, 3 of which were intradermal vaccine only, with different levels and/or lengths of use of the suction device. There were 17 people in the group that also had an intranasal dose. About a third of them experienced nasal or respiratory reactions, like a runny or blocked nose, or wheezing.

Only 1 of the 17 people in the nasal vax group reported a Covid infection, while 16 of the 53 in the other groups did. No one became ill enough from Covid to require hospitalization. While this represented a reduced rate of Covid after nasal booster, this isn’t strong evidence of protection against infection as it relies on people reporting infections, not routine testing of all participants – and there was no placebo nasal spray group. Signs of mucosal immunity weren’t reported in the clinical trial. However, the preclinical study showed signs of increased mucosal immunity after intranasal vax – though there wasn’t a study of whether vaccinated animals transmitted the virus.

There was no mention in the report, or at the company’s website, on whether the intranasal version of the vaccine will go into phase 2 trial.

Understanding how intranasal Covid vaccination affects immunity: A study of monoclonal antibodies after vaccination from the University of Toyama (Japan)

This paper reports on in-depth analyses of the impact of intranasal Covid vaccination on S-IgA (immunoglobulin secreted by mucosal tissues). To do this, they developed over 200 monoclonal antibodies from plasma cells in mucosal and non-mucosal tissues of nasally-immunized mice. They also tested S-IgA as prophylaxis in Covid-infected hamsters – and the treatment reduced the weight loss caused by the illness.

This work provides insight into the “precise contribution and molecular nature of multimeric secretory IgA induced by intranasal vaccines.” Although even the many plasma cells they recovered don’t provide enough cells for a comprehensive analysis of all immunity response, the developers were able to shed light on how intranasal vaccination induces both mucosal and systemic antibody responses.

Other preclinical reports for mucosal vaccines

• Intranasal protein subunit vaccine from the University of Oslo (Norway): This is the first report I’ve seen for this vaccine. The vaccine uses an engineered albumin to deliver the adjuvanted vaccine to mucosal tissues. The vaccine was tested in mice, including a challenge test with SARS-CoV-2. An influenza version of the vaccine was also tested with influenza challenge. Control animals were either unvaccinated, or intranasally vaccinated with protein subunit without the other vaccine components. Unlike the control animals, the mice receiving the full vaccine were protected against signs of disease and less virus was detected in their mucosal tissues. The developers also compared mice intranasally vaccinated with full vaccine with mice injected with the BNT/Pfizer mRNA vaccine, and concluded signs of systemic immune response were similar.

• Intranasal protein subunit vaccine from the University of Ottawa (Canada): This is the first report I’ve seen for this vaccine. It was tested as a booster in mice that were first injected with monovalent or bivalent mRNA vaccine, comparing that regimen with mRNA boosters. The developers tested signs of immune response, and concluded that an intranasal booster based on the Beta variant broadened immune response after monovalent mRNA vaccine, but not bivalent mRNA vaccine.

• Live attenuated virus vaccine from the Friedrich Loeffler Institute (Germany) and University of Bern (Switzerland): The first preclinical report for this vaccine included a transmission test in hamsters, finding minimal signs of virus in nasal washing, and none in organs. Now named OTS-228, the new report describes experiments in hamsters aiming to assess safety of the attenuated virus, including at very high doses. Transmission tests were also done, again finding complete protection against lung infection (from Alpha and Delta variants). The developers concluded that vaccinated animals weren’t transmitting any live virus from the vaccine, even at artificially high doses.

• Intranasal protein subunit vaccine from Yale University and Xanadu Bio (USA): This new report is the second describing experiments in mice with an intranasal unadjuvanted intranasal subunit vaccine booster after an mRNA injection. (The first is here, where the vaccine was described as one against sarbecoviruses.)

• Intranasal protein subunit vaccine developed at Guangzhou Medical University (China): This is a bivalent vaccine, incorporating subunits for original SARS-CoV-2 and an Omicron variant (BQ.1.1). A new report describes tests in mice and hamsters with both injected and intranasal versions of the vaccine, including viral challenges and transmission studies. Intranasal vaccination provided more protection from infection in challenge tests, and reduced transmission.

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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.
• 34 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. They are mostly viral vector vaccines.
• In addition to the 5 authorized mucosal vaccines, 5 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, and finished recruiting by early 2025.

• Phase 2b (“mini-efficacy”) for the intranasal protein subunit vaccine from Castlevax – this grant was paused and may be terminated;
  
• Phase 2b for the intranasal live attenuated vaccine from Codagenix (not started);
  
• Phase 2b for the oral viral vector vaccine from Vaxart (trial start announced at the end of September 2024; trial registration here) – this grant was not cancelled and the trial is proceeding; and
• Phase 2b for the intranasal viral vector vaccine from Blue Lake Biotech/CyanVac (trial started in December 2024, trial registration here).

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Durable or “variant-proof” vaccine news

This month there is news on a couple of vaccines in this category: Kostaive, Arcturus’ self-amplifying mRNA vaccine, and the Geovax vaccine for people with immunocompromise.

Next Kostaive applications for regulatory approval

Kostaive is the first next-generation Covid vaccine approved by stringent drug regulatory authorities – it has been approved in Japan and the European Union. The manufacturers announced that they expect to file an application for marketing approval in the UK this quarter. They also report that a US FDA application has been planned for soon after.

Geovax trial plans and new preclinical results

Geovax’s Project NextGen grant was terminated. The latest update from the company on trials of their viral vector vaccine for people with immunocompromise: They are still recruiting people with blood cancer to their phase 2 trial at various locations in the US (details here), and people with chronic lymphocytic leukemia (CLL) to their phase 2 trial in Los Angeles (details here). The first readout of results from their phase 1 trial in healthy adults is expected soon.

The vaccine is based on modified Ankara virus (MVA), targeting several SARS-CoV-2 proteins (S, M, and E). It was developed at the City of Hope with the NIH’s National Cancer Institute (NCI), to better serve immunocompromised people on cancer treatment. Early clinical results for this vaccine have been encouraging. This month, they published their 7th preclinical study report. The report describes experiments in mice, receiving 1 or 2 doses, with some unvaccinated control mice. In a challenge test with the Beta variant, all control mice became ill and died. No vaccinated animals lost weight and died. Minimal disease was detected in the mice receiving 1 dose, and the boosted mice showed no signs of disease.

(All records for this vaccine here.)

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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), trade name Kostaive: This self-amplifying mRNA vaccine was authorized in Japan in November 2023, with rollout in October 2024. It was also authorized for Europe in February 2025.

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);

• Funding was terminated for the Phase 2b (“mini-efficacy”) trial for GeoVax (viral vector vaccine).

Note: Gritstone Bio was originally in line for a phase 2b trial for their self-amplifying mRNA vaccine. However, the company declared bankruptcy and in January 2025, their assets were sold.

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Pancoronavirus vaccine news

Another pancoronavirus vaccine is going into clinical trial – the 7th to reach first-in-human study. There were 4 preclinical study reports for 3 vaccines in this category this month. Not included in this section is a second preclinical report for the intranasal protein subunit vaccine from Yale University and Xanadu Bio (listed above in mucosal vaccines). Although their first report described the vaccine as aiming at sarbecoviruses generally, this wasn’t mentioned in the new report.

Phase 1 trial for the protein subunit vaccine from Duke University (USA)

A trivalent version of this vaccine, based on components of SARS-CoV-2, the original SARS, and MERS, induced signs of immune response to all these coronaviruses in preclinical studies. However, the version going into trial, named Cov-RBD-scNP-001, includes only SARS-CoV-2. The phase 1 trial has been registered, ahead of recruitment. Up to 51 participants will receive 2 doses of the vaccine, in one of 3 doses. Locations for recruiting people for this trial haven’t been announced yet.

(All records on this vaccine here.)

Preclinical studies:

2 reports for an intranasal protein subunit vaccine from the China Cuba Joint Innovation Center: These 2 bring the number of preclinical reports for this vaccine to 6. In the first, the developers describe tests in mice, concluding that although there were signs of immune response to both original SARS and MERS, neutralizing capacity was very low in one type of test.

The second new report describes tests of 2 versions of the vaccine (PanCoV1 and PanCoV2) in monkeys. Both versions include S and N SARS-CoV-2 proteins, and an adjuvant. However, in PanCoV2, the N protein is fused to the S protein (a chimeric protein). There were 3 animals in each of 3 groups – one for each of the vaccines, and a group receiving only the adjuvant. Animals got 3 intranasal doses. Blood samples were checked for signs of reactivity to the Delta variant of SARS-CoV-2, the original SARS, MERS, and HCoV-229E (an alphacoronavirus that can infect humans and bats). One of the animals in the PanCoV1 group showed low immune responses. Signs of immune response were stronger for PanCoV2, and maintained at the last testing (4 months after the last dose). The vaccine was also able to generate signs of mucosal immunity.

(All records for this vaccine here.)

Viral vector vaccine from Johns Hopkins University (USA): This is the first report I’ve seen for this vaccine. The vaccine is based on SC2, an immunogen constructed from non-Spike components of SARS-CoV-2 that also appear in other coronaviruses, with a combination of vectors. The report describes experiments in mice, hamsters, and rhesus macaques, including an Omicron challenge test in hamsters, and Delta challenge in the primates. In the primates, the developers tested a heterologous regimen, using one each of 3 vectors instead of the full combination. The vaccines protected the animals in both of the challenge tests.

Protein subunit vaccine from the Chinese Academy of Sciences Key Laboratory of Pathogen Microbiology and Immunology (China): This is the first report I’ve seen for this vaccine. The vaccine builds on a vaccine that is authorized in China, ZF2001. (All records on ZF2001 here.) This version of the vaccine includes proteins from both SARS-CoV-2 and the original SARS, including a version where the SARS-CoV-2 component was the Beta variant. The vaccines were tested in mice. The developers tested for signs of immune response to SARS-CoV-2 variants, SARS, and 6 other coronaviruses. Mice got 3 doses of the vaccine, and the developers also tested it as a booster after an inactivated Covid vaccine. The developers found stronger immune responses to SARS-CoV-2 and SARS than the other coronaviruses.

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. Of these vaccines, 7 have reached 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.
  
  
• Duke University (USA) – protein subunit.
  
  
• INSERM/Ennodc (formerly LinkInVax) (France) – protein subunit.
  
  
• Osivax (France) – protein subunit.
  
  
• * 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 or approved by drug regulatory agencies designated stringent, or listed, by WHO – in bold. Authorization is pending in the European Union. I’ve listed the vaccines in 2 categories, in order of date of first authorization (or initial approval).

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).
• Kostaive (LUNAR-COV19) (USA): Japan (November 2023), European Union (February 2025).

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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 4,089 in the Ad5-nCoV arms. (Previously in preprint.)	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. Short protocol. Began enrolling in March 2025.
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). Results.	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. 875 previously vaxed people were boosted with iNCOVACC, Covaxin (inactivated vax) or Covishield (AstraZeneca viral vector vax). Not large enough to detect a difference in immune response. Lower rate of adverse reactions than Covishield.
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). Phase 2b.
dNS1-RBD (Pneucolin) Viral vector (influenza) Beijing Wantai BioPharm (China) (All records)	Intranasal.	Phase 1. Phase 2. Joint results. Phase 1 (age 3-17). 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.
FINCoVac Viral vector (adenovirus) Rokote Laboratories (Finland)	Intranasal.	Phase 1, 2nd registry record.
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).
* GLS-5301 DNA GeneOne Life Science (South Korea)	Intranasal.	Phase 1. Results.
LVT001 Protein subunit LovalTech (France)	Intranasal.	Phase 1/2.
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

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), Ingenza USA, UK Mosaic-8b	Protein subunit Beta	Non-primate Non-primate Primate, non-primate Non-primate (previously in preprint) Non-primate (previously in preprint) Primate and non-primate
Charité Universitätsmedizin Berlin Germany NILV-PanCoVac	Viral vector All	Non-primate (mucosal)
China Cuba Joint Innovation Center China, Cuba PanCoV1, PanCoV2	Protein subunit Sarbeco	Non-primate (mucosal) Non-primate (mucosal) Non-primate (mucosal) Non-primate (mucosal) * Non-primate (mucosal) * Primate (mucosal)
* Chinese Academy of Sciences Key Laboratory of Pathogen Microbiology and Immunology China Unnamed	Protein subunit Sarbeco	Non-primate
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 Cov-RBD-scNP-001	Protein subunit Beta	Primate Primate, non-primate Non-primate (previously in preprint) Primate, non-primate	US government grant terminated in March 2025. * Phase 1 trial. (Up to 51 people in the US) Not yet recruiting.
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 (formerly Emergex) UK/USA CoronaTcP	Protein subunit Beta		Phase 1 trial (26 participants in Switzerland) Results. (Formerly preprint) 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/Ennodc (formerly LinKinVax) France PanCov (CD40.CoV2/RBDv)	Protein subunit Sarbeco	Non-primate Primate, non-primate Primate Non-primate (conference poster) Non-primate	Phase 1/2 trial (Up to 240 participants in France) Booster trial; began recruiting in May 2024.
* Johns Hopkins University USA Unnamed	Viral vector Sarbeco	Primate, non-primate
Mynvax Private India Unnamed	Protein subunit Sarbeco	Non-primate
National University of Singapore Singapore Clec9A-RBD	Protein subunit Sarbeco
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
Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Fudan University China rTTV-RBD-HA2	Viral vector Beta (plus influenza)	Non-primate (mucosal)
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 Non-primate (There was also a paper about this vaccine’s development in 2021.)	US government grant terminated in March 2025.
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 (previously in preprint)	US government grant terminated in March 2025.
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.
Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan Canada Unnamed	Protein subunit Sarbeco	Non-primate
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 Sarbeco	Non-primate * 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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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.)