Pancoronavirus Vaccines Update: Lots of Preclinical Results & Another Trial Underway

In my last post, I looked at the landscape for intranasal and other mucosal Covid vaccines, with the big news of White House funding boost for next generation Covid vaccines. That includes pancoronavirus vaccines as well – vaccines that aim to protect against more coronaviruses than the one that causes Covid.

Last year, a group (including Anthony Fauci) wrote that universal coronavirus vaccines are “an urgent need”. We’ve had fatal coronavirus outbreaks from 3 coronaviruses in the last 20 years – MERS and the pair of SARS – and there’s a reservoir of more of them in bats that have “been increasingly spilling over into humans and other mammals,” they wrote.

A counterpoint from Barney Graham: There’s no guarantee that such a vaccine would actually work against whatever specific coronavirus next crosses over. If it might at best “hold the fort” until a specific vaccine was developed, he said, vaccine platforms that can adapt quickly to a new virus are more critical. I think holding the fort in the first few months is a very big deal, though – and a pancoronavirus vaccine might be able to be adapted, too.

A year ago, WHO’s chief scientist reckoned we’d have a pancoronavirus vaccine in 2 years. Back then, a couple of candidates had fully recruited phase 1 trials. But neither group of developers has reported the results, so that prediction is looking over-optimistic now.

Deciding which vaccines to include here was complex. There are vaccines aiming to be essentially variant-proof for SARS-CoV-2, the virus that causes Covid, and ones that are aiming to target coronaviruses more broadly. It’s hard to work out, though, which side of this blurry divide to put some vaccines on. In the end, I decided to include vaccines where the developers say they are explicitly targeting coronaviruses more broadly than SARS-CoV-2, and have tested for signs of response to non-SARS-CoV-2 coronavirus(es).

That leaves out a small group of vaccines that may not be all that different to some that are included here – and far more advanced. In particular, there’s the UB-612 booster from Vaxxinity (USA). That aims to be variant-proof and more durable than current vaccines, and it’s reached phase 3: Results from phase 2 have recently been published. The company is reported to be planning to apply for authorization of this booster in Australia and the UK this year.

In the end, I found preclinical results for 17 vaccines that met my criteria, 2 of which started phase 1 trials in 2021. Late in 2022 a phase 1 trial got underway for another of them. There are other pancoronavirus projects with no results released yet, including several getting funding support from major players. I haven’t seen a comprehensive tracker for them.

The 17 vaccines included in this post are targeting:

• 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).

The post starts with an overview summarizing progress and related news, with detail on trials and preclinical results in later sections:

• Overview
• Clinical trial progress
• Recent results
• Addendum: Table of 17 vaccines with preclinical results

Overview

I looked for preclinical results and clinical trials of vaccines which explicitly target coronaviruses more broadly than SARS-CoV-2, and have tested for responses to non-SARS-CoV-2 coronavirus(es). I found 17 vaccines with at least one set of results for preclinical studies released, 3 of which are also in phase 1 trials. They are mostly protein subunit vaccines. Here’s a breakdown of them by their coronavirus targets and vaccine type:

	Preclinical results	Clinical trial status
Vaccines	17	3 in phase 1
Target	Sarbecoviruses (7) Betacoronaviruses (5) All (or unspecified) (5)	Betacoronaviruses (2) All (1)
Vax type	Protein subunit (12) mRNA (2) Viral vector (1) Virus-like particle (1) Protein subunit + DNA boost (1)	Protein subunit (1) mRNA (1) Virus-like particle (1)

• Since late July 2022, I’ve found 12 reports of preclinical research for 10 of these vaccines. Several showed immune responses in animals in challenge tests with multiple coronaviruses, including human and animal coronaviruses.
• 2 of the 3 vaccines in phase 1 trials were fully recruited by the end of 2021, but no results have been released. The first of those was developed by the US Walter Reed Army Institute of Research (WRAIR) – and I’ve seen no report on what’s happening.
• The second is the needle-free mRNA vaccine from DIOSynvax, a biotech spin-off from Cambridge University. In December, they entered into a partnership with a company specializing in mRNA, Ethris (Germany) – so presumably they are still modifying the vaccine.
• The latest phase 1 trial was registered at the end of 2022, and fully recruited by February 2023. It’s for an enveloped virus-like particle vaccine from VBI Vaccines (Canada), targeting coronaviruses generally.
• Caltech’s Mosaic-8b vaccine has several preclinical reports, and it’s poised for a clinical trial. However, the developers report that because their innovative vaccine has so many components, there are challenges manufacturing enough high quality vaccine for a trial.

In other news:

• There’s a good post by Kate Kelland about pancoronavirus vaccines from the Coalition for Epidemic Preparedness Innovations (CEPI), a global public/private vaccine partnership. There’s also a good article by Jon Cohen about the challenges developers are facing, and another on next generation vaccines by Ewen Callaway.
• The US company, Vaxart, has an oral viral vector vaccine in phase 2 trial, and had planned a human challenge trial for it this year. However, they have now reportedly put that vaccine on hold, turning their attention to developing an oral panbetacoronavirus vaccine instead.
• Codiak BioSciences began proceedings in bankruptcy court. They are one of the companies supported by CEPI’s panbetacoronavirus program. The company had presented preclinical results of their vaccine at the 2022 Word Vaccine Congress, but I haven’t found a publication. It was developed with the Ragon Institute (including MIT and Harvard). I don’t know where this leaves that vax.

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Clinical trial progress

Since my last post on these vaccines, another has entered clinical trial, bringing the total to 3 in phase 1 – all of which are fully recruited. It’s an enveloped virus-like particle vaccine developed by VBI Vaccines (Canada), targeting coronaviruses generally. The phase 1 trial of a booster for 103 previously vaccinated people began in Canada in October 2022. In February, the developers noted it was fully recruited.

There’s still no report of results for either of the first 2 pancoronavirus vaccines – even though they were both fully recruited by the end of 2021. So reports from both teams are long overdue.

The first into clinical trial was a protein subunit vaccine from the Walter Reed Army Institute of Research (USA) targeting betacoronaviruses. A phase 1 trial for 29 people began in the US in April 2021 – by September, it was fully recruited. A few months later, the results were described as “positive”, but haven’t been released. The BBC reported that a phase 2 trial was expected.

The second into clinical trial was a needle-free mRNA vaccine from DIOSynvax, a spin-off company from Cambridge University (UK), targeting betacoronaviruses. That phase 1 trial for 36 people began in the UK in December 2021. It was fully recruited quickly. In December, it was reported that DIOSynvax had partnered with a German company specializing in mRNA, Ethris, to develop a panbetacoronavirus vaccine through to phase 1/2 trial.

I haven’t seen a report of any other pancoronavirus vaccine about to launch into clinical trial. However, Caltech’s panbetacoronavirus vaccine, Mosaic-8b, is apparently ready for clinical tests. The developers have released results for preclinical studies in several species, including non-human primates. The leader of the team said last year that their plan was to study Mosaic-8b as a boost after a Covid vaccine before starting a human trial. In February, they released a preprint for preclinical experimentation that fits that description.

In that preprint they write that there is a catch, though. Manufacturing enough of their vaccine for clinical trials is challenging, “because of the need to produce 9 different components (8 RBDs and SpyCatcher003-mi3) at Good Manufacturing Practice (GMP) level.” I haven’t seen a pharmaceutical manufacturer mentioned as a partner yet for this vaccine.

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Recent results

You can see all the results I’ve found for these 17 vaccines in the table below this post.

The vaccines from the Walter Reed and Caltech in the US have released several preclinical studies recently, including using their pancoronavirus vaccines as boosters for other Covid vaccines. For Walter Reed, that was the Johnson and Johnson vaccine, and for Caltech, it was a SARS-CoV-2-specific vaccine from their lab.

Some other vaccines with notable results (in alphabetical order by developer):

• At the end of July 2022, UK’s Francis Crick Institute published preclinical results in mice for a combination of a primary protein subunit vaccine with a DNA boost based on a different SARS-CoV-2 subunit to the prime shot. Antibodies were able to neutralize a variety of animal and human coronaviruses, and the vaccine provided protection against SARS-CoV-2 in a challenge test.
• China’s Fudan University has developed a protein subunit vaccine, CF501, targeting sarbecoviruses, publishing results of primate and non-primate studies last year. Another paper in March reported on tests of serum of vaccinated macaques against recent Omicron variants. Antibodies could neutralize the variants tested in the lab, though neutralization of BQ.1.1 and XBB was much lower.
• In January, we saw results of tests of an authorized Covid vaccine from a group adapting it to develop a pansarbecovirus vaccine. That vaccine is a protein subunit vaccine, GBP510, trademarked SKYCovione, from SK Bioscience (South Korea). It was developed with the Universities of Washington and North Carolina at Chapel Hill (USA). The developers reported the current vaccine was able to provide some protection for mice against challenges with several coronaviruses. The planned pansarbecovirus vaccine is called GBP511.
• In November 2022, the PanCorVac group from the University of Wisconsin-Madison published results of tests of protein subunit vaccine in hamsters and mice. Lab tests showed antibodies could recognize SARS, as well as SARS-CoV-2. Vaccinated animals had reduced signs of virus when challenged with Covid variants (Beta, Delta, and Omicron) and a pangolin coronavirus.
• At the end of October 2022, a group from Yale University published results of their intranasal protein subunit booster in hamsters and mice after primary vaccination with the BNT/Pfizer mRNA vaccine. They reported signs of mucosal immunity against SARS as well as SARS-CoV-2.

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Addendum: 17 vaccines with preclinical results

* Indicates new entry this post.

Developer Country Vaccine name	Type of: Vaccine Coronavirus	Preclinical results	Clinical trial status
California Institute of Technology (Caltech) USA Mosaic-8b	Protein subunit Beta	Non-primate * Non-primate * Non-primate Primate, 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 Beta	Non-primate	Phase 1 trial (incl. protocol) (Up to 36 participants) Began December 2021. Fully recruited.
Duke University USA RBD–scNP	Protein subunit Sarbeco	Primate Primate, non-primate (* formerly preprint)
* Francis Crick Institute UK (Unnamed)	Protein subunit with DNA boost All	Non-primate
* Fudan University China CF501	Protein subunit Sarbeco	Primate, non-primate Primate Primate
INSERM Vaccine Research Institute France CD40.CoV2	Protein subunit Sarbeco	Non-primate * Primate
Pennsylvania State University USA (Unnamed)	Protein subunit All	Non-primate (* formerly preprint)
* 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.)
* University of North Carolina at Chapel Hill (Unnamed)	Viral vector Sarbeco	Non-primate
* University of Toronto Canada (Unnamed)	Protein subunit Sarbeco	Non-primate
* University of Wisconsin-Madison (PanCorVac) (Unnamed)	Protein subunit All	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.)
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.
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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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.

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.)