More Progress on Next Generation Covid Vaccines, and a Setback in the US (Update No 35)

Image credit

Cartoon by Hilda Bastian, CC BY-NC-ND 4.0

Last month’s update ran long, so this one covers less than a month – but there’s still a lot of news. There are new immune response results from a clinical trial. And there is a brief report suggesting that a durable vaccine for people with immunosuppression provides some cross-protection against monkeypox.

There was good news for access to an updated self-amplifying mRNA vaccine from Arcturus in Japan – and bad news for access to it for the foreseeable future in the US thanks to changes in regulations there. Vaccines will probably be facing extraordinary hurdles there for as long as the US government travels in this direction.

On the plus side, we heard that another of the Project NextGen-funded trials will be completed. Good news, too, for a mucosal vaccine from the US, with a new pharma partner that might see the vaccine through phase 3 trials and beyond. A couple of phase 1 trials for intranasal vaccines have moved a step forward – one in France, and one in the US. Plus, there are 9 preclinical reports.

As usual, I have the post broken down into 3 categories of next-generation vaccines (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?”

• 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

• Postscript: US Project NextGen funded trials

Mucosal vaccine news

This month, there is good news about 3 clinical trials for mucosal vaccines, and that starts this section. I also added 4 new preclinical reports for mucosal vaccine, plus a report from 2024 that I had previously missed.

Clinical trial and development progress

• Intranasal vaccine from the NIAID (USA): Last update, I reported that a phase 1 trial for an intranasal versus intramuscular fusion protein vaccine called Boost-2867 was registered, but not yet recruiting. The 6 sites in the US that will be running this vaccine have now been posted, with Pittsburgh and San Francisco listed as already recruiting. The sites and contact details are here.

• Intranasal vaccine from Lovaltech (France): This is another fusion protein vaccine, called LVT001. I reported on this a few months ago. This vaccine was developed with public funding, a university, and the national health agency, and has a partnership with a major pharmaceutical company – which one is still not public. In a preclinical transmission test, vaccinated animals were protected and did not transmit the virus to co-housed animals. The company reported on social media that the first stage of their phase 1 trial had completed successfully: Participants received the lowest dose in May, and the trial is progressing.

• Oral vaccine from Vaxart (USA): This vaccine fell victim to the US government’s retreat from Project NextGen. Vaxart was the first to start a “mini-efficacy” phase 2b trial under that Project. The company announced a deal with Dynavax to carry the vaccine forward after phase 2, depending on clinical trial results. If all goes well, Dynavax would be licensed to take the vaccine into phase 3 trial and have the right to apply for marketing approval internationally.

Preclinical results for mucosal vaccines

• Viral vector vaccine from Castlevax and Icahn School of Medicine Mt Sinai (USA): This vaccine is in clinical trials. It is a version of the Mt Sinai-developed vaccine, NDV-HXP-S, which has also been the basis for several vaccines internationally. (All records on the Castlevax version here.) The vaccine’s vector is live attenuated Newcastle Disease Virus. This new preclinical report describes the development of a technique to test for virus shedding, which is theoretically possible after using live attenuated vaccines intranasally. The sequencing technique was tested on a prototype trivalent version of the Castlevax vaccine. The developers report that it could be used to test for vaccine shedding in vitro and in clinical trials.
  
  I also added a preclinical report for this vaccine from last year. This describes tests of intranasal versions adapted to Omicron BA.1 and BA.5 in mice. All the mice vaccinated with BA.1 were protected in a BA.1 challenge test, but virus was detected in one of the mice vaccinated with BA.5. The developers also report on the results of an intranasal boost with the vaccines, after previous mRNA vaccination.
  

• Intranasal NDV-HXP-S and injected viral vector vaccine from the National Center of Biotechnology (CNB-CSIC) (Spain): The CNB-CSIC vaccine is based on modified virus Ankara (MVA). It has been tested in several preclinical studies in both intramuscular and intranasal versions. (All records on the MVA vaccine in my collection here.) This new report describes tests in mice and hamsters of 4 regimens: homologous tests of 2 doses of the injected MVA vaccine or the Mt Sinai-developed viral vector vaccine, NDV-HXP-S; or heterologous vaccination, with an injected or intranasal prime, followed by the other as a booster. In a challenge test, all the vaccinated mice did not show signs of illness, while a control group of unvaccinated mice did.
  
  The same process was also done with hamsters, with several from each group co-housed with healthy unvaccinated hamsters to test for transmission. None of the hamsters co-housed with vaccinated animals showed signs of illness; 3 out of 4 co-housed with intranasally-vaccinated hamsters had no detectable virus, and none of the hamsters in the intranasal prime followed by injection boost group did. Intranasally-vaccinated hamsters had better protection of their upper respiratory tracts. However, the numbers were too small to conclude that an intranasal-first regimen is more likely to protect against transmission.
  

• Intranasal protein subunit vaccine from the State University of New York at Buffalo and Texas Biomedical Research Institute (USA): This is the first report for this vaccine. The developers describe tests of a regimen of 2 intranasal doses in mice. In a Covid challenge test, none of the control group of unvaccinated animals survived, but all the vaccinated mice did, without signs of illness.

• Intranasal protein subunit combined influenza/Covid vaccine from the Chinese Academy of Science Key Laboratory of Pathogen Microbiology and Immunology (China): This is the first report for these chimeric vaccines, which combines components of influenza and SARS-CoV-2. One is an injected mRNA vaccine, and the other is an intranasal protein subunit booster. The prime-boost regimen was tested in mice, including both adjuvanted and unadjuvanted versions of the intranasal vaccine, and a challenge test with H1N1 influenza (but not Covid). The developers concluded that the vaccines elicited strong immune responses against both diseases, and protected against influenza in the challenge test.

• Intranasal protein fusion vaccine from Harvard Medical School and National Emerging Infectious Diseases Laboratories (NEIDL) (USA): This is the first report for this vaccine. The developers report tests in mice of a 2-dose regimen of either injections of the vaccine, or injection followed by intranasal boost. Injection-only vaccination protected mice in a low-dose Covid challenge test, but not against high-dose challenge, whereas intranasally-vaccinated mice were protected in both.

Skip ahead to next news category

Mucosal Covid vaccine overview

• 5 mucosal vaccines are currently authorized for use, at least 1 in each of 6 countries. None have been authorized by a drug regulatory agency designated stringent, or listed, by WHO. However, each has been authorized by a regulator which has transitional WHO listing for vaccines.
• 36 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, 6 have reached phase 2 trials, and another 2 have reached phase 2/3 trial.

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Durable or “variant-proof” vaccines

This month, there is a brief report about cross-protection against monkeypox for a vaccine in this category, good news about one of the Project NextGen-funded phase 1 trials, and 3 preclinical reports. There were also more results from a phase 3 trial of Kostaive, the self-amplifying mRNA vaccine developed by Arcturus. In addition, Meiji Seika Pharma markets the vaccine in Japan, and recently rolled out a version adapted for the JN.1 variant XEC.

There was also bad news about the Arcturus vaccine. The plan had been to apply for US approval this year. However, Arcturus announced in November that this was now off because of “sudden changes in regulatory requirements by the FDA for COVID-19 vaccines.” Meanwhile, CSL, an Australian drug company, will be marketing Kostaive in Asia and Europe. Marketing approval has been applied for in the UK.

Clinical trial news

• More results from a phase 3 trial for the Arcturus self-amplifying mRNA vaccine (Kostaive): One of the phase 3 trials for this vaccine tested it against the BNT/Pfizer mRNA vaccine as a booster in Japan (trial register entry). Clinical results have already been reported, showing a more durable response from the self-amplifying mRNA vaccine. A new report describes analyses of antibody responses undertaken to explore why these were more durable with the samRNA. The authors concluded that their “results support a model whereby prolonged antigen expression and presentation moves immune profiles towards activating phenotypes with broad antigenic coverage.” (All phase 3 results for this vaccine here, or see the summary in the European Medicines Agency assessment report.)

• News on the STX vaccine from Capricor (USA): I added this vaccine to this category because a phase 1 trial was funded by the US government Project NextGen. I reported on the vaccine and the start of the phase 1 trial in my August update. This month, the company announced that the trial is continuing, with results anticipated in the first few months of 2026. (All records for this vaccine here.)

Preclinical reports (including some brief clinical results)

• Viral vector vaccine from GeoVax (USA): I added a full report and a conference abstract for this vaccine. It is based on modified Ankara virus (MVA), and was developed at the City of Hope with the NIH’s National Cancer Institute (NCI), to better serve immunocompromised people on cancer treatment. The vaccine is in several clinical trials. (All records for this vaccine here.)
  
  The full report describes tests in mice. The vaccine includes both S and N proteins. The full vaccine was tested, as well as versions containing only S or N. Only the full vaccine provided full protection in challenge tests with B.1 and an Omicron variant (XBB.1.5). The developers reported that, “Despite full protection, no neutralizing antibodies were detected against XBB.1.5 in the sera of GEO-CM04S1-immunized animals, suggesting a critical role of T-cell responses.”
  
  The conference abstract briefly reports on cross-protection for monkeypox from this coronavirus vaccine. The preclinical part involved testing for signs of immunity to monkeypox in non-human primates, as well as a monkepox challenge test in mice. The clinical data apparently came from some participants in a phase 2 trial for people with cancer and immunosuppression (hematologic malignancy, after cell transplantation and CAR-T therapy). In that clinical trial, people with cancer experienced similar results with the GeoVax vaccine to healthy people vaccinated with the BNT/Pfizer vaccine. In humans and animals, the GeoVax vaccine appeared to induce some immunity to monkeypox.
  

• Viral vector vaccine from Betuvax, Swiftgen, and Artgen Biotech (Russia): This is the first report in my collection for this vaccine. It is based on an adeno-associated virus (AAV) vector. The developers tested 3 different Covid antigens in their AAV vaccine in mice – full-length spike protein, S1 truncated subunit, and receptor-binding domain (RBD). Only the full-length spike elicited strong neutralizing antibody responses.

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 1 authorized vaccine in this category, and it has been authorized by a drug regulatory authority designated by WHO has stringent, and tested against an mRNA vaccine (Kostaive):

• 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. Application for authorization in the UK planned next.

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Pancoronavirus vaccine news

This month, there was one preclinical report for a vaccine in this category:

Nanoparticle adjuvant for pancoronavirus vaccine from the University of Texas at Austin (USA)

This is the first report for this adjuvant in a vaccine. There was a previous report of an earlier version. Covid vaccines have typically targeted the S1 protein, which has limited the breadth and durability of immune response. The developers report on using an adjuvant TLR7-NP in a pancoronavirus vaccine. The adjuvant aims to improve lymph node targeting and activation of S2-specific cells, and the developers report that it was able to do this in mice. They found signs of coronavirus immune response in mice who had either vaccine with TLR7-NP or their earlier version of TLR7 to SARS-CoV-2, the original SARS, MERS, and 2 other human coronaviruses (HCoV-HKU1 and HCoV-NL63).

The developers also report on tests of TLR7-NP adjuvanted vaccine compared to mRNA vaccine, again studying signs of immune response to those 5 coronaviruses. Antibody responses were higher for the pancoronavirus vaccine than the mRNA vaccine. The mice vaccinated with mRNA vaccines could not develop high antibody responses to HCoV-HKU1 and HCoV-NL63.

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, 8 have reached phase 1 clinical trials, and 1 has reached phase 2, 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.
  
  
• SK Bioscience (South Korea) – protein subunit (trial pending).
  

• * VBI Vaccines (Canada) – eVLP. [This company announced bankruptcy in late 2024.]

• * Walter Reed Army Institute of Research (WRAIR, USA) – protein subunit.

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Addendum 1: List of authorized next generation Covid vaccines (with countries)

There are 7 next-generation Covid vaccines authorized in 7 countries. Only one has been approved by drug regulatory agencies designated stringent, or listed, by WHO – in bold; the others have all been approved in at least one country by a drug regulator WHO has listed with transitional status for vaccines. 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).

Durable or “variant-proof”:

• Gemcovac (India), self-amplifying mRNA vaccine: India (June 2022).

• Kostaive (LUNAR-COV19) (USA), self-amplifying mRNA vaccine: 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.) 450 people in China (Phase 4). Results.	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. 450 people: Convidecia showed less antibodies and higher mucosal signs of immunity than an mRNA vaccine. Waning at 6 months was similar for both.
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). Results. 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.
Boost-2867 Fusion protein NIH’s National Institute of Allergy and Infectious Diseases (NIAID) (USA) (All records)	Intranasal.	Phase 1. * Recruitment began in November 2025.
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 Biotech (USA) (All records)	Intranasal.	Phase 1. Results (formerly in 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.		* First stage (lowest dose) completed in May 2025.
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 (terminated because of difficulty recruiting). Results, results.
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). Phase 2a.
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. (Previously available in preprint.)
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.
WSK-V106C Viral vector Sichuan University (China) (All records)	Intranasal.	Phase 1. Results.
(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.) Initial group of 5,000 participants to proceed, but government funding for continued recruitment cancelled (August 2025).

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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
Acuitas Therapeutics (Canada) (Unnamed)	mRNA Sarbeco	Primate, 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
Burnet Institute Australia Unnamed	Sarbeco	Non-primate
California Institute of Technology (Caltech), Ingenza USA, UK Mosaic-8b	Nanoparticle mosaic Beta	Non-primate Non-primate Primate, non-primate Non-primate (previously in preprint) Non-primate (previously in preprint) Primate and non-primate Non-primate (previously in preprint)
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 (previously in preprint) (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 Non-primate	US government grant terminated in March 2025. Phase 1 trial. (Up to 51 people in the US) Began July 2025.
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 Non-primate (mucosal)
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)
Harvard T.H. Chan School of Public Health USA (Unnamed)	Nanoparticle mosaic SARS-CoV-2, alpha	Non-primate
Korea Research Institute of Bioscience and Biotechnology South Korea (Unnamed)	Protein subunit Sarbeco	Non-primate
INSERM Vaccine Research Institute/Ennodc (formerly LinKinVax) France EDC.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	Non-primate Non-primate (mucosal)
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
Rockefeller University USA (Unnamed)	Nanoparticle mosaic Sarbeco	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) Phase 1/2 trial announcement	More on plans for adapting this vaccine – GBP510 authorized as SKYCovione. See the University of Washington research listed below in this table.
Stanford University/DXVX USA/South Korea DX-DRG-B05	Virus-like particle Beta	Non-primate Primate Erratum (correction to legend in a figure). Non-primate Non-primate (previously preprint)	Phase 1 clinical trials completed in the US (registered here) and South Africa (registered here), and planning underway for phase 2 trials in 2026 in South Korea, elsewhere in Asia, and the US.
State Key Laboratory of Respiratory Disease Guangzhou Medical University China (Unnamed)	Protein subunit Sarbeco	Primate and non-primate
Sun Yat-Sen University China FP-HR5-NP	Protein subunit Sarbeco	Non-primate (mucosal) Non-primate (mucosal)
Sun Yat-Sen University/Guangzhou Medical University China 3Rs-NC	Protein subunit Sarbeco	Non-primate (mucosal)
Tiba Biotech USA (Unnamed)	Self-amplifying mRNA, protein subunit Sarbeco	Non-primate
University College London UK ZRS	Protein subunit Sarbeco	Non-primate
University of Alberta Canada (Unnamed)	Peptide subunit All	Non-primate (mucosal) Non-primate (mucosal)
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 (previously in preprint) Non-primate (previously in preprint) (There was also a paper about this vaccine’s development in 2021.)	US government grant terminated in March 2025.
University of California Irvine/Techimmune USA (Unnamed)	mRNA All	Non-primate (mucosal) Non-primate Non-primate Non-primate
University of Hong Kong China IBIS	Live attenuated Sarbeco	Non-primate (mucosal)
University of Houston/Auravax USA NanoSTING-NS	Protein subunit (intranasal) Sarbeco	Non-primate Non-primate Non-primate Primate, non-primate
University of Leiden/Immunetune BV Netherlands CoVAX	DNA Sarbeco	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 (Previously in preprint)
* University of Texas at Austin USA TLR7-NP	Nanoparticle Sarbeco, Beta	Non-primate
University of the Chinese Academy of Sciences/Wuhan YZY Biopharma China (Unnamed)	Protein subunit All	Non-primate (mucosal)
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 Washington and University of North Carolina at Chapel Hill USA (Unnamed)	Nanoparticle Sarbeco	Primate, non-primate
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.
  

• Pancoronavirus vaccines aim to protect against coronaviruses more broadly – sometimes called “universal coronavirus vaccine.” These 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 MERS as well as the sarbecoviruses), or
  
  – up to the whole coronavirus family, which 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 in the design of the vaccine, 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.)

Postscript: US Project NextGen funded trials

Mucosal vaccines:

• 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 for the oral viral vector vaccine from Vaxart (trial start announced at the end of September 2024; trial registration here) – further recruitment for this trial was cancelled, though followup will be completed for the participants already dosed (around 5,000). The company has a deal with Dynavax to take the vaccine forward, depending on phase 2 trials.
• Phase 2b for the intranasal viral vector vaccine from CyanVac/Blue Lake Biotech (trial started in December 2024, trial registration here) – no recent news on this trial.

• 2 trials are apparently not going ahead: A Phase 2b (“mini-efficacy”) for the intranasal protein subunit vaccine from Castlevax – this grant was paused and may be terminated. Castlevax has since registered a far smaller phase 2a trial with some similar methodological features. Another for the intranasal live attenuated vaccine from Codagenix had not apparently started.

Durable or “variant-proof” vaccines:

• Phase 1 for STX from Capricor (trial began dosing participants in August 2025). Capricor announced in November 2025 that the trial is ongoing.

• Phase 1 for TNX-1800 from Tonix (aiming for lifelong immunity) (planned to go into clinical trial in 2024 – no recent news);

• 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.

Pancoronavirus vaccines – presumed canceled:

• CoronaTcP (Gylden Pharma, UK/US) – protein subunit.
• Unnamed (PopVax, India) – mRNA.

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