One of the critical ways a next generation Covid vaccine can improve on the original vaccines is to be more durable and…
Authorization Milestone for First NextGen Covid Vaccine in Europe and More News (Update 24)
The first next-generation Covid vaccine is on its way to authorization in the European Union. Recently rolled out in Japan, the self-amplifying mRNA (saRNA) vaccine from Arcturus now has the critical approval it needs from the European Medicines Agency. The vaccine’s “official” name is now zapomeran, with the trade name, Kostaive. More on that, and the next steps for this vaccine, in the “variant-proof” vaccine section below. Plus, now that access for a saRNA vaccine is on the way in so many countries, check out my companion post, too: An introduction to saRNA.
Some mucosal vaccines have also reached important earlier milestones this month. An intranasal vaccine has begun recruiting in the US for its Project NextGen-funded phase 2b “mini-efficacy” trial. It’s the second: The first has now fully recruited its initial safety group. And there’s another preclinical study showing an intranasal vaccine preventing transmission of Covid infection. There’s news as well on the human challenge study in the UK.
I begin this month with several items of news for Project NextGen. 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:
- Another December post, “Getting ready for more mRNA fear-mongering: A compendium”
- 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 Project NextGen
Second phase 2B “mini-efficacy” trial underway and registered
The phase 2b trial for CVXGA is now registered and recruiting. This intranasal vaccine was developed by the University of Georgia (USA), and is being manufactured by Blue Lake Biotech/CyanVac. It is a viral vector vaccine, based on PIV5 (parainfluenza 5). It’s the second Project NextGen-funded “mini-efficacy” to be registered.
CyanVac announced that the first participant had received a vaccine dose. The trial is following the same process as the first of these trials. They plan to recruit 400 participants as a sentinel cohort to closely assess safety. 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.
They are currently recruiting in Sacramento, California, with Lafayette in Louisiana coming next. If you are interested in joining this trial, there is a phone number and email contact here.
(All records in my collection for this vaccine here.)
Milestone reached for the first Project NextGen-funded “mini-efficacy” trial
This month, Vaxart announced that they have fully recruited the 400-participant sentinel group. Now they are waiting on 30-day results, to determine if the full trial of their oral Covid vaccine will proceed.
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. This month, Vaxart announced that they have fully recruited the 400-participant sentinel group. Now they are waiting on 30-day results, to determine if the full trial will proceed.
(All records for the Vaxart vaccine in my collection here.)
Other news
- GeoVax is a viral vector vaccine developed at the City of Hope with the NIH’s National Cancer Institute (NCI), to better serve immunocompromised people on cancer treatment. It’s in the durable “variant-proof” nextgen category. A spokesperson reported to a conference that their Project NextGen-funded phase 2b trial is planned for 2025.
- Back in June, Swiss biotech Rocketvax announced they had Project NextGen funding to run a phase 1 trial of their intranasal Covid vaccine. They have now announced a partnership with the Dutch manufacturer, HALIX for the vaccine. This might become the 32nd mucosal Covid vaccine to head into clinical trial.
- There was another Project NextGen funding announcement this month. The Fred Hutch Cancer Center will provide the centralized T-cell immune assays for the Project NextGen trials.
Mucosal vaccine news
This month, the only clinical trial news is above in Project NextGen news: The start of the phase 2b “mini-efficacy” trial for the intranasal vaccine from Blue Lake Biotech/CyanVac, and the critical milestone for the one for Vaxart’s oral vaccine. In other news, the early human challenge study project in the UK has expanded to London. And I added 4 preclinical study reports – including one showing prevention of transmission of the Covid virus in hamsters for another of the Project NextGen-funded vaccines (Castlevax).
Second site recruiting for the early human challenge study project for mucosal vaccines
In my August post, I reported on the COV-CHIM 02 study recruiting participants in Oxford. It’s a critical step to enable human challenge trials of mucosal vaccines, which would dramatically speed up their development.
The first step was deciding which Covid variant to use, and then developing a version that is infectious enough to work for a trial, with the lowest risks. COV-CHIM 02 tests a version of Omicron BA.5. There is now a second site for the study: Imperial College London is now recruiting participants for COV-CHIM 02 in London.
New preclinical studies for mucosal vaccines
I added 4 new preclinical studies this month. One is a pancoronavirus vaccine, so it is summarized in that section. The other 3 included 2 with a track record, and 1 new vaccine:
- Intranasal Castlevax vaccine (USA) adapted for Omicron prevented transmission: This is the viral vector vaccine – based on Newcastle Disease Virus – developed by Icahn/Mt Sinai. A phase 2b “mini-efficacy” trial funded by Project NextGen is planned. It is also being developed in several lower-income countries, as it is licensed for those developers on a non-profit. This new report describes a version adapted for the XBB.1.5 Omicron variant, tested in mice and hamsters. It includes a matched-variant challenge (XBB.1.5) in both species. A vaccine based on the original Covid strain did not protect against infection from the Omicron variant, but the vaccine adapted to that variant did.
The developers also did a transmission study in the hamsters. (They wrote that hamsters are better suited for this as they are more susceptible to Covid infection.) Hamsters vaccinated with the active vaccine and then challenged with the Omicron variant were co-housed for 4 days with those in a control group (vaccinated with the vector part of the vaccine only).
In the Omicron-adapted vaccine group, none of the hamsters or the unvaccinated animals they were co-housed with had any signs of infection. However, in the group vaccinated only with the original version of the vaccine, half had signs of infection, and all the unvaccinated hamsters co-housed with them had infectious virus in their upper and lower airways.
(All records in my collection for the Castlevax vaccine here. Clinical trials for other versions of this vaccine in the table below this post.)
- AAHI’s (USA) intranasal protein subunit vaccine compared to injected, and injected saRNA: The Advanced Health Institute (AAHI) in Seattle developed the protein subunit vaccine that was rolled out as Indovac in Indonesia (my records for that vax here). They also developed an saRNA vaccine (my records for that vax here). In this new report, the developers describe a version of the protein subunit vaccine with an adjuvant, testing both it and the original version in mice intranasally and intramuscularly. A lyophilized (dried) version was also tested. They also compared 2 injected doses of the adjuvanted version with 2 injections of their saRNA vaccine, and prime-boost regimen of both (with protein subunit first in one group, and saRNA first in another).
The best results came from injected saRNA prime with protein subunit boost. The developers also report that the intranasal version showed higher responses in some immune responses, but lower in others. (They did not test intranasal protein subunit after saRNA as the primary dose.)
- Intranasal vs intramuscular comparison for a viral vector vaccine developed at King Abdulaziz University (Saudi Arabia): This is the first report I’ve seen for this vaccine. It’s called rAd5-SARS2-S1, and it is based on an adenovirus. Intranasal and injected versions were tested in mice and hamsters. There was a challenge test in hamsters, which found greater protection for 2 doses of intranasal vaccine than intramuscular.
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. 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 (trial started in December 2024, trial registration here).
Durable or “variant-proof” vaccine news
Although there were no new reports of results in this category, it has this month’s biggest news: Authorization is pending in the European Union for the saRNA vaccine developed by Arcturus Therapeutics (USA).
The active substance in this vaccine now has an official international non-proprietary name, zapomeran, and an international trade name, Kostaive. On December 12, the European Medicines Agency (EMA) recommended authorization for the vaccine in adults.
Once EMA has recommended authorization, the European Commission has 67 days to issue the marketing authorization. That means authorization for this vaccine is due by the end of February 2025. European authorization is valid for all 27 EU countries as well as those in the European Economic Area (Iceland, Liechtenstein, and Norway). When the marketing authorization is issued, the EMA publishes its full assessment report for the drug.
In the meantime, there are 22 records in my collection for this vaccine, and you can see them here. They include close to 20,000 participants in phase 3 trials, which I summarized here, here, and here. Some highlights:
- In a small head-to-head study in Japan, signs of immune response to Omicron were better for the Arcturus vaccine than for the BNT/Pfizer vaccine, with similar responses to other strains in the short-term.
- For all the strains tested in that study at 12 months, the rate of immune response for the Arcturus vaccine was substantially higher than for the BNT/Pfizer vaccine, though it had waned a little between 6 and 12 months.
- The amount of mRNA in the Arcturus vaccine is lower than for standard mRNA: 5μg compared to 30μg in the BNT/Pfizer vaccine.
- The frequency of adverse reactions to this vaccine was similar to current Covid mRNA vaccines, but the rate of severe reactions was lower. In a head-to-head booster trial, the rate of severe reactions was 2% for the Arcturus vaccine compared to 4% for the BNT/Pfizer vaccine. (In other studies, the rate of severe fatigue, for example, was 10% for the Moderna vax.)
What next for this vaccine? In my January 2024 post, I reported on what I knew then. Arcturus had also had discussions with the UK regulators. In addition, Arcturus has a licensing partnership for this vaccine with Australia’s international vaccine biotech, CSL Seqirus – a deal that, along with potential saRNA influenza vaccines, could end up being worth billions. In their 2024 annual report to investors, CSL Seqirus reports that they plan to lodge an application to the FDA for a version of the vaccine updated for variants in 2025. That was before the US election, and the worrisome announcements about nominees for US health agencies.
In my October post, I wrote about the scare campaign against saRNA mounted in Japan when this vaccine rolled out. With the vaccine heading for international rollout, I decided I would get ready for the anti-vax campaigns sure to come elsewhere with a post on saRNA. I realized, though, that had to start with a deep dive into fear-mongering about mRNA vaccine that accompanied the current vaccines. That pair of posts is online now:
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), trade name Kostaive: This self-amplifying mRNA vaccine was authorized in Japan in November 2023, with rollout in October 2024. It was also approved by the European Medicines Agency in December 2024, with authorization for the European Union pending.
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) (planned to go into clinical trial in 2025).
These trials have not been registered at ClinicalTrials.gov as yet.
Pancoronavirus vaccine news
Pancoronavirus vaccines aim to provide protection not only from variants of the SARS virus that causes Covid, but also against the next new coronavirus to spread among humans. This month, I added 2 preclinical reports to this category, including a mucosal vaccine that aims to protect against coronaviruses and influenza.
New preclinical results
- PanCov, the protein subunit vaccine developed by INSERM (France): This vaccine aims to protect against sarbecoviruses (the coronavirus group that includes Covid and the original SARS). The manufacturers, Ennodc (formerly LinkInVax), began recruiting participants for a phase 1/2 trial in May 2024. There have been several preclinical reports for this vaccine, in primates as well as in non-primates.
The vaccine targets both Spike and N proteins. The new report tested T cell response to the vaccine in 2 species of mice. The authors concluded that the vaccine is capable of stimulating long-lasting T-cell immunity.
- A viral vector vaccine with intranasal boosts developed by Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences (China): This vaccine is based on a pox virus, vaccinia. It is aimed at betacoronaviruses and influenza. It’s called rTTV-RBD-HA2. This first preclinical report tests the vaccine in mice. The developers had previously developed an experimental combined Covid and influenza vaccine based on an adenovirus.
This vaccinia-based vaccine includes components from 5 viruses: Omicron variant of the Covid virus, original SARS, MERS, and 2 strains of influenza. The developers compared a course of 3 injections with an injection followed by 2 intranasal boosts. A control group was vaccinated with the viral vector alone. The developers tested for signs of immune response to all 5 of the viruses, and carried out challenges of Covid and influenza.
The developers detected both antibodies and T-cell responses to all 5 of the viruses in vaccinated mice. Only the mice receiving intranasal boosts showed signs of mucosal immunity, though antibodies were lower. The intranasal-boosted group also had the best protection in the challenge tests.
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, 6 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.
- 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.
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), initial European approval, authorization pending (December 2024).
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). *Phase 2b. | ||
| 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.) |
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/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. |
| 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 (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 |
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).
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):
- Mucosal vaccines (March 2022)
- Pan-SARS-Cov-2 and pancoronavirus (July 2022)
- Mucosal vaccines (July 2022)
- Mucosal vaccines (September 2022)
- Mucosal vaccines (April 2023)
- 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.)