A Major First Next Generation Covid Vaccine: Could There Be More in 2024? (Update 13)

A next generation vaccine has been authorized by a major drug regulator for the first time. It’s based on a next generation mRNA, called self-amplifying messenger RNA (SAM, or samRNA). SAM doesn’t just leave a message and disappear, the way current mRNA vaccines do. It makes copies of itself inside our cells – similar to the way a virus works. Theoretically, leaving a blueprint behind enables longer-lasting immunity than mRNA can offer. There’s a small amount of evidence showing immune effects of this new vaccine from Arcturus Therapeutics are durable to at least 12 months. Called LUNAR-COV19, it was authorized in Japan late last year.

In this update, I’m starting with vaccine rollout – where else this new vaccine might be authorized this year, and which vaccine might be next. After that, I have recent results broken down into 3 categories of next-generation Covid vaccines (definitions below). The trials for LUNAR-19 are in the “durable” category below, including a recent small head-to-head trial between the LUNAR-COV19 and Pfizer vaccines.

• Rollout overview
• Mucosal vaccine news
• Durable or “variant-proof” vaccine news
• Pancoronavirus vaccine news
• Addendum 1: List of authorized vaccines (with countries)
• Addendum 2: Table of mucosal vaccines in clinical trials
• Addendum 3: Table of pancoronavirus vaccines with results
• Addendum 4: Definitions of vaccine types

Rollout overview

The self-amplifying mRNA (SAM) vaccine from this post’s introduction is a vaccine developed by Arcuturus Biopharmaceuticals in the US. It was authorized by Japan in November 2023, making it the first next generation vaccine to get the nod from a drug regulatory agency designated stringent or listed by WHO.

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

Another 6 Covid vaccines have been authorized in 6 countries, and I’ve listed them below this post, including where they were authorized and when.

One of them is the first SAM authorized, Gemcovac. Like Arcturus’ LUNAR-COV19 vaccine, it was developed by a US company (HDT Bio). They licensed it to a company in India, Gennova in India. It was authorized in India in June 2022 in a trial run by Gennova comparing it with the Oxford/AstraZeneca vaccine. I pointed out some limitations of that evidence here.

The 5 other authorized vaccines are mucosal vaccines – either inhaled or intranasal, including 4 viral vector vaccines and a protein subunit vaccine. They have each been authorized in one or 2 countries: China, India, Indonesia, Iran, Morocco, and Russia.

The next mucosal vaccine on the rollout horizon could potentially be from the US company, Codagenix. A single dose spray of this vaccine has been in phase 2/3 as part of the large placebo-controlled WHO Solidarity Trial for Vaccines since August 2022. And there will be a large phase 2b trial as part of Project NextGen in the US this year. A spokesperson for the company has said they hope to be ready to submit to the FDA this year.

Another Covid vaccine that has a mucosal version may be getting close to authorization, though it’s not clear if that would include the intranasal booster. Called Patria, it’s a version of the Mount Sinai/Castlevax vaccine, developed in Mexico by Avi-Mex.

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Mucosal vaccine news

I didn’t find any new clinical results for mucosal Covid vaccines in the last month or so. However, a phase 1 trial of an intranasal protein subunit vaccine developed by Intravacc (Netherlands) is now fully recruited, with results expected soon.

In addition, CyanVac updated the phase 2 trial record of their intranasal viral vector vaccine in late December. They now expect the trial to be fully recruited in April, with 400 participants receiving doses.

I’ve added 10 preclinical reports on results for mucosal vaccines to my collection. These include:

• A study at Beth Israel Deaconess Hospital in New York found “near complete protection” from Omicron challenge (BQ.1.1) in rhesus macaques after intratracheal administration (into the windpipe) – both intranasal and intramuscular administration weren’t as effective.
• A viral vector vaccine (MVA) developed by the Centro Nacional de Biotecnología (CNB CSIC) in Madrid was adapted to the Beta variant. In a study comparing this with the original version in mice, a single intranasal dose protected against lethal Beta variant challenge as well as 2 intramuscular doses. There were also signs of immunity to a range of Covid variants.
• A study in hamsters by a team from Duke-NUS Medical School and the National University of Singapore compared intranasal doses to injections, and reported that immune system effects after the intranasal version lasted longer, and showed responses to more variants

See also the section on pancoronavirus vaccines, which includes news on another 2 intranasal vaccines.

Mucosal Covid vaccine overview:

• Mucosal vaccines are currently authorized for use in 6 countries.
• 27 have reached clinical trial, with at least one of those has been discontinued. These are tracked in a table below.
• 6 mucosal vaccines have reached phase 3 trials, including the 5 authorized vaccines.

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Durable or “variant-proof” vaccine news

This is a rather vague category, including vaccines that aim to be more durable. I don’t include a table for tracking these vaccines. That’s because while I’m quite confident I’ve tagged all the vaccines in my collection that fall into the other 2 categories of next generation vaccines, I’m not sure how many can be classified as aiming to be “variant-proof”.

The big news this update is LUNAR-COV19, the recently authorized SAM from Arcturus. I’ve included an overview of all the clinical trials for this vaccine, including one published in December. After that, there are 2 new preclinical studies for other vaccines.

LUNAR-COV19 (Arcturus, USA):

This SAM vaccine has been adapted for recent variants, but the version that has been authorized is an earlier one, called ARCT-154. You can dig into all the records in my collection for all versions here.

Overview of the trials for the LUNAR-COV19 series:

• Phase 1 and 2 trials of an earlier version, ARCT-021, in Singapore, with 42 and 64 participants respectively (published December 2022).
• A phase 2 trial of ARCT-021, in Singapore and the US, with 581 participants. Unpublished (trial registry record).
• A phase 1 to 2 trial of 3 versions as a booster, ARCT-021, ARCT-154, and ARCT-165, in Singapore and the US, with 72 planned participants. There is a poster of results for 36 participants, 12 for each vaccine, suggesting immune response is durable to at least a year (September 2023).
• A phase 1 to 3 trial of ARCT-154, in Vietnam, with around 1,000 in earlier phases and over 16,000 in the placebo-controlled efficacy part of the trial. Preprint (September 2023).
• A phase 3 immunogenicity and safety trial of ARCT-154 as a booster, in Japan, with 828 participants randomized to a LUNAR-COV19 or BNT/Pfizer booster (published December 2023, previously a preprint, July 2023).

The trial in Vietnam is this vaccine’s efficacy trial. It was placebo-controlled, running during Delta and Omicron waves in Vietnam. Of the over 16,000 participants, 17% were aged 60 or over, and 35% of the participants under 60 had co-morbidities.

There were 2 injections, 28 days apart. Efficacy:

• Any confirmed Covid: 56.6% (95% CI: 48.7–63.3).
• Severe Covid: 95.3% (80.5–98.9), with 2 in the vaccine group and 41 in the placebo group.
• Death from Covid: 86.5% (-7.4–98.3), with 1 death in the vaccine group and 9 in the placebo group.

The rate of systemic adverse events was close to 50% for the first dose in phase 3, and close to 75% in the earlier phases – and lower for the second dose. That was roughly similar to the BNT/Pfizer and Moderna trials, but the rate of severe events was less than 1%. For context, the most common severe event for BNT/Pfizer was 4% for fatigue; for Moderna, it was 10% for fatigue.

In the head-to-head randomized booster trial, the participants had all had 3 doses of either BNT/Pfizer or Moderna mRNA vaccines: 420 got a LUNAR-COV19 booster (5 μg) and 408 a BNT/Pfizer one (30 μg). Almost all were under 65 years of age (98%) and had had their 3rd mRNA shot 5 or more months previously (98%). Most had been fully vaccinated with BNT/Pfizer (80%), and all but 1 of the rest had 2 doses of Moderna followed by a BNT/Pfizer booster.

The rate of systemic adverse events was similar (66% for LUNAR-COV19 vs 63%). The rate of severe adverse events was 2% for LUNAR-COV19 and 4% for BNT/Pfizer.

The measures of immune response for LUNAR-COV19 at 28 days were non-inferior for the original Covid strain compared to BNT/Pfizer, and superior for Omicron BA.4/5.

We don’t have durability data yet for any of the large trials. Durability for the head-to-head trial will be reported later for 3, 6, and 12 months after vaccination.

Preclinical studies for other vaccines:

• TU88mCSA and ALCmCSA, mRNA vaccines from Tufts University (USA): In this paper, the group reports a high level of protection against Omicron variants in hamsters, including lower viral load in the upper airways.
• GLB-Cov2-043, an mRNA vaccine from GreenLight Biosciences (USA): A study in mice and hamsters, including Omicron challenge. (All records on the GLB-Cov2 vaccines.)

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Pancoronavirus vaccine news

Background re-cap:

We’ve had major human epidemics or pandemics of 3 dangerous coronaviruses – 2 types of SARS, plus MERS. There are many other coronaviruses circulating among animals, too. Pancoronavirus vaccines aim to provide protection not only from variants of the SARS virus that causes Covid, but also some against the next new coronavirus that’s likely to spread among us.

Pancoronavirus vaccines aren’t as far along the development path as the other categories above. A table below this post keeps track of those with publicly available preclinical results. As far as I know, there are still only 3 vaccines in this category in phase 1 trials, with a fourth planned to start in early 2024:

• DIOSynVax (Cambridge University spin-off, UK);
• INSERM (France) – not yet underway;
• VBI Vaccines (Canada); and
• Walter Reed Army Institute of Research (WRAIR, USA).

New this update:

Duke University’s protein subunit vaccine: In a new preclinical study, the team reports the results of testing a modification of the vaccine in primates and non-primates. I have also added a 2021 paper I had missed, in which the vaccine is studied in primates.

University of Washington’s protein subunit vaccine (with SK Bioscience): There’s a new report of testing design modifications in mice for this vaccine. A study previously available in preprint has now been published. In 2022, this group had hoped to be in a first-in-human clinical trial by the end of 2023 – I haven’t seen a report of their current timetable.

NILV-PanCoVac, an intranasal viral vector vaccine from Charité Universitätsmedizin Berlin: This vaccine is new to my list, but the study isn’t new – I had missed a publication from July 2023. This reports on an early study in hamsters, with a SARS-CoV-2 challenge test after a single low dose.

Finally, a preclinical study that was previously available as a preprint is now published, for the intranasal viral vector vaccine from the University of California Irvine and Techimmune.

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

There are now 7 next-generation Covid vaccines authorized in 7 countries. Only one has been authorized by a drug regulatory agency designated stringent or listed by WHO – I’ve marked that with an asterisk*. I’ve listed the vaccines in 2 categories, in order of date of first authorization.

Mucosal:

• Razi Cov Pars (Iran), intranasal protein subunit vaccine: Iran (October 2021).
• Sputnik (Russia), intranasal viral vector vaccine: Russia (April 2022).
• Convidecia (China), inhaled viral vector vaccine: China (September 2022), Morocco (November 2022), Indonesia (March 2023).
• iNCOVACC (USA/India), intranasal viral vector vaccine: India (September 2022).
• Pneucolin (China), intranasal viral vector vaccine: China (December 2022).

Self-amplifying mRNA:

• Gemcovac (India): India (June 2022).
• LUNAR-COV19 (USA): Japan* (November 2023).

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Addendum 2: Table of mucosal vaccines in clinical trials

* Indicates new entry since my 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 2 (aged 6-17 years). Booster adapted for variant.	10,420 people in China (Phase 3). Results. 1,350 people (Phase 3). 540 people, in Malaysia (Phase 3). 904 people in China (Phase 4). Results. 360 people (Phase 4). 451 people (Phase 4). Results.	904 people: Comparison after 2-dose course of inactivated vax: Convidecia injection vs inhaled, protein subunit, or CoronaVac booster (Phase 4 results). Both injected & inhaled Convidecia had stronger impact on signs of immunity than the others; response after inhaled version was slower but longer-lasting than injected (which peaked then declined from day 14), better for Omicron though not as good for original virus. No measure of mucosal immunity used. 451 people: Comparison of different versions adapted for variant, including a bivalent version. Booster of inhaled Convidecia after previous vaccination with inactivated vaccine. Signs of immune response to Omicron were higher for the bivalent vaccine, though lower for the original SARS-CoV-2 strain.
Ad5-S Viral vector (adenovirus) State Key Laboratory for Infectious Disease/Guangzhou Enbao Biomedical Technology Co (China) (All records)	Intranasal.	Infection prevention study.
Ad5-triCoV/Mac & ChAd-triCoV/Mac Viral vector (adenovirus) McMaster University/Canadian Institutes of Health Research (Canada)	Aerosol.	Phase 1.
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).
Avacc 10 Protein subunit Intravacc (Netherlands) (All records)	Intranasal.	Phase 1. * (Fully recruited, completion expected early in 2024.)
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.
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. (Protocol.)
CVXGA1-001 Viral vector (parainfluenza) CyanVac/Blue Lake Tech (USA) (All records)	Intranasal.	Phase 1. Phase 2.
DNS1-RBD (Pneucolin) Viral vector (influenza) Beijing Wantai BioPharm (China) (All records)	Intranasal.	Phase 1. Phase 2. Joint results.	30,990 participants in Colombia, Philippines, South Africa, Vietnam. Results (previously in preprint.) 5,400 participants in Ghana (Phase 3).	Comparison of 2 doses of intranasal vaccine 14 days apart, with placebo control, during circulation of Omicron. Included >13,000 previously unvaccinated people. Efficacy shown 90 days after 2nd dose. There was some decline at 180 days. Efficacy against symptomatic Covid: No previous vax: 55.2% (CI 13.8 to 76.7) Inactivated: 38.2% (CI -49.2 to 74.4) Viral vector: 39.9% (CI -16.7 to 69.1) mRNA: 10.1% (CI -45.9 to 44.5) Efficacy against severe Covid: No previous vax: 66.7% (CI 8.3 to 87.9) Inactivated: 54.6% (CI -47.3 to 86.0) Viral vector: 50.0% (CI -6.8 to 76.6) mRNA: 19.5% (CI -39.2 to 53.4) Efficacy against hospitalization: 100% (CI -9.2 to 100) Adverse events were very low – similar to placebo. Less than 8% of people had a runny and/or blocked nose or sore throat.
GAM-COVID-VAC (rAd26-S – Sputnik Light) Viral vector (adenovirus) Gamaleya Research Institute (Russia)	Intranasal.	Phase 1/2	7,000 participants in Russia (Phase 3 or phase 2/3 – not clear).
Mambisa Protein subunit Centre for Genetic Engineering & Biotechnology (CIGB) (Cuba) (All records)	Intranasal drops.	Phase 1/2. Phase 1/2. Results (report of a conference presentation). Phase 2.
MV-014-212 Viral vector (RSV) Meissa Vaccines (USA) (All records)	Intranasal drops or spray.	Phase 1. Results (press release).
MVA-SARS-2ST Viral vector (MVA) German Centre for Infection Research (DZIF)/IDT Biologika (All records)	Inhalation.	Phase 1.
NDV-HXP-S Viral vector (Newcastle Disease Virus) Castlevax/Icahn Mt Sinai (All records)	Intranasal.	Phase 1. Results (press release).
Patria (NDV-HXP-S/AVX-COVID-12-HEXAPRO) Viral vector (Newcastle Disease Virus) Laboratorio Avi-Mex (Mexico) (All records on Patria, see NDV-HXP-S above for early development.)	Intranasal.	Phase 1. Results. Phase 2. Results (press release).	Phase 2/3 for injected version only. Results (press release without data).
PRAK-03202 Protein subunit Oravax (USA) [Oravax was established by OraMed (Israel) to develop this vaccine, using Premas Biotech’s PRAK-03202 and their oral vaccine technology] (All records on oral PRAK-03202, and on intramuscular version)	Oral.	Phase 1 (in South Africa). Results (press release only).
Razi Cov Pars Protein subunit Razi Vaccine & Serum Research Institute (Iran) (All records)	Intranasal (third dose after 2 injections).	Phase 1. Results. Phase 2. Results. Phase 1 to 2 (in 12-17 year-olds). Phase 4 (Booster). Phase 1 to 2 (in 5-17 year-olds).	41,128 people in Iran, comparing the 3-dose course to 2-dose inactivated Sinopharm Beijing vax (Phase 3). (Press report of results, in the first 24,000 participants.)	There were no hospitalizations for Covid in the Razi Cov Pars group and 5 in the Sinopharm group. The rate of Covid was reportedly more than twice as high in the Sinopharm group.
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.
(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. (Recruiting: started October 1, 2021.) Results (press release).	Omicron adaptation was developed for an Omicron challenge trial, originally planned for second half of 2023. This vax is now on hold, as Vaxart is trying to develop an oral pan-betacoronavirus vaccine.

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Addendum 3: Pancoronavirus vaccines with preclinical results

* Indicates new entry since previous update post.

Developer Country Vaccine name	Type of: Vaccine Coronavirus	Preclinical results	Clinical trial status
Academia Sinica Taiwan (Taiwan) (Unnamed)	mRNA All	Non-primate
Beijing University of Chemical Technology (China) (Unnamed)	Live attenuated pangolin coronavirus All	Non-primate
California Institute of Technology (Caltech) USA Mosaic-8b	Protein subunit Beta	Non-primate Non-primate Non-primate Primate, non-primate
* Charité Universitätsmedizin Berlin Germany NILV-PanCoVac	Viral vector All	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	Phase 1 trial (incl. protocol) (Up to 36 participants) 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
Guangdong Pharmaceutical University China (Unnamed)	Protein subunit All	Non-primate
INSERM Vaccine Research Institute/LinKinVax France PanCov (CD40.CoV2)	Protein subunit Sarbeco	Non-primate Primate, non-primate Primate Non-primate (conference poster)	Phase 1 clinical trial planned for early 2024.
Oragenics/Inspirevax/ National Research Council of Canada USA, Canada NT-CoV2-1	Protein subunit (Intranasal) All	Non-primate (original vax) Non-primate (original vax)
Osivax France OVX033	Protein subunit Sarbeco	Non-primate
Pennsylvania State University USA (Unnamed)	Protein subunit All	Non-primate
Scripps Research Institute USA (Unnamed)	Protein subunit Beta	Non-primate
SK Bioscience/ Uni of Washington/Uni of North Carolina at Chapel Hill South Korea, USA GBP511	Protein subunit Sarbeco	Primate, non-primate (testing Covid vaccine GBP510 against other sarbecoviruses)	More on plans for adapting this vaccine – GBP510 authorized as SKYCovione. See the University of Washington research listed below in this table.
Stanford University USA DCFHP-alum	Protein subunit Sarbeco	Primate Erratum (correction to legend in a figure). Non-primate
Sun Yat-Sen University China Unnamed)	Protein subunit Sarbeco	Non-primate
University of California Irvine/Techimmune USA (Unnamed)	Viral vector Beta	Non-primate * Non-primate (mucosal) (previously in preprint) (There was also a paper about this vaccine’s development in 2021.)
University of North Carolina at Chapel Hill USA (Unnamed)	Viral vector 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	(See “GBP511” above in this table.)
University of Wisconsin-Madison (PanCorVac) USA (Unnamed)	Protein subunit All	Non-primate Non-primate Non-primate
VBI Vaccines Canada VBI-2901	eVLP All	Non-primate Non-primate (Press release)	Phase 1 trial (103 participants) 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 1B-06-PL	Protein subunit Beta	Non-primate Non-primate Non-primate (incl RFN) Non-primate Primate Primate Primate (with J&J vax)	Phase 1 trial (29 participants) Began April 2021. Results described as “positive” – no data reported yet. Additional detail on phase 1 trial.
Walter Reed Army Institute of Research (WRAIR) USA RFN	Protein subunit Beta	Non-primate (incl SpFN) Primate
Yale University USA (Unnamed)	mRNA All	Non-primate Non-primate
Yale University/Xanadu Bio USA (Unnamed)	Protein subunit, intranasal booster Sarbeco	Non-primate

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Addendum 4: Definitions of vaccine types

• Mucosal vaccines: These enter the body the way the virus does – through mucosal tissues. It’s hoped that provides defence against infection. They can be administered via different routes – squirts or drops in the nose, inhaled through the mouth through a nebulizer (similar to an asthma medication), or in tablet, capsule, or sublingual form.
• Pan-SARS-CoV-2 or “variant-proof” vaccines: These aim to provide protection against any variant of the coronavirus that causes Covid-19 – including future variants. I include vaccines that aim for greater durability in this group.
• Pancoronavirus can be targeted to:
  • the “subgroup” the 2 SARS viruses came from (the sarbecovirus subgenus),
  • coronaviruses from the next level up (the genus, betacoronavirus, which includes lethal diseases like MERS, as well as common cold viruses), or
  • the whole coronavirus family – it has 4 genuses, including betacoronavirus and alphacoronavirus (with more common cold viruses).

I classify a vaccine as a pancoronavirus one when the developers are explicitly targeting coronaviruses more broadly than SARS-CoV-2, and have tested for signs of response to non-SARS-CoV-2 coronavirus(es) (or clearly plan to).

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

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For details on how I track Covid vaccine progress, see my background post. Notes on my collection of studies are here. The collection is in a public Zotero library you can dig into here.

Previous update posts on next generation Covid vaccines:

1. Mucosal vaccines (March 2022)
2. Pan-SARS-Cov-2 and pancoronavirus (July 2022)
3. Mucosal vaccines (July 2022)
4. Mucosal vaccines (September 2022)
5. Mucosal vaccines (April 2023)
6. Pancoronavirus vaccines (April 2023)
7. Next generation (May 2023)
8. Next generation (June 2023)
9. Next generation (July 2023)
10. Next generation (August 2023)
11. Next generation (September 2023)

All my Absolutely Maybe Covid-19 vaccine posts

All previous Covid-19 posts at Absolutely Maybe

My posts at The Atlantic, at WIRED, and debunking posts at my personal website.

Disclosures: My interest in Covid-19 vaccine trials is as a person worried about the virus, as my son is immunocompromised: I have no financial or professional interest in the vaccines. I have worked for an institute of the NIH in the past, but not the one working on vaccines (NIAID). More about me.

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