The Pan-Coronavirus Vaccine Landscape

What sort of progress is being made on pancoronavirus vaccines?

Well, a little bit of progress, anyway?

We’ve written about efforts for a pan-coronavirus vaccine here a couple times before (here, here). Since a pan-coronavirus vaccine could go a long way towards renormalizing life, let’s check in and see what (if any) progress has been made.

A survey of pan-coronavirus vaccine efforts

Our first stop, and indeed inspiration, is to check in with the awesome med-chem blogger Derek Lowe, at In the Pipeline, hosted at Science Translational Medicine. ^[1] He wrote a nice little survey of the state of the field, starting out with a few general words about the structure of the families of coronaviruses.

So many of them seem to be related to bats… why?!

Side trip: why so many viruses from bats?!

First, I’d always wondered what in the world is wrong with the dang bats?! Why are they so loaded up with viruses, including SARS-CoV1 and 2? The science explainers at SciShow on YouTube offer some explanations:

• 1/5th of all mammal species today are bats, so there are just a lot of them, and they pose a large attack surface for infections.
• They’re the only mammals who can do truly self-powered flight (not counting humans with our wacky flying machines). To fly in a 1 gravity field with a thin atmosphere takes a lot of power, and many compromises in other areas.
• They’re basically bags of germs, having transferred at least 12 viral diseases to humans! (Mostly our fault of course, for disturbing their habitat.)
• That’s related to a flight adaptation: they have hyperactive mitochondria to generate energy, but that leaves lots of reactive oxidative species (ROS) around to cause various bits of biochemical havoc, including DNA damage.
• To defend themselves from DNA damage-caused cancers, they have super-duper DNA repair mechanisms and prevention of damaged cells from replicating.
• But DNA damage can come from viral infection, too, which is why it triggers inflammation. To keep that down, bats use their repair mechanisms to fix damaged DNA, but dampen inflammation (notably STING proteins, and PYHIN proteins).
• So, because they dial back inflammation, they’re infested with lots of viruses.
• But… they also don’t get sick much from those viruses. We don’t completely know why, but they do have really active interferon systems to repair DNA, and that also helps clear virus infections. Also, something something ribonuclease L. Basically, they have really weird immune systems!
• And with all that, there’s some evidence viruses have learned to go dormant in bats until an opportune moment arises.

So… lots of complications, but bottom line: flight adaptation takes energy, that can lead to DNA damage, so super DNA repair and anti-inflammation mechanisms allow viruses in and weird immune systems keep them from getting sick.

Moral: Don’t disturb the bats.

Structure of the coronaviruses

Derek goes on to tell us how the coronaviruses come in α, β, γ and δ families, all with funny pseudo-Graeco-Latin names. The nasties are mostly in the β coronavirus family. Shown here is a cladogram from a paper in 2019 ^[2] that gives you some idea of the complexity. (Click to embiggen. Since it’s from 2019, SARS-CoV2 is of course not there yet.) Many originate in bats, some in birds, some in camelids, and one in beluga whales.

With that structure in mind, Derek then divides potential vaccines into 4 groups, depending on how general their protection is:

Type I Vaccines: generate immunity to all four genuses of coronavirus

Type II Vaccines: generate immunity to the betacoronaviruses

Type III Vaccines: generate immunity to the sarbecovirus (lineage B) betacoronaviruses

Type IV Vaccines: generate immunity to current and future variants of just the particular sarbecovirus we’re dealing with, SARS-CoV-2.

So what progress is there?

That then shifts our focus to a paper in Nature Reviews Drug Discovery ^[3] which more or less surveys the field. Since a lot of these are very early efforts, while there are a couple ‘real’ papers, much of the “references” are to mere corporate press releases (and in 1 case, an actual advertisement!).

Reading them is, frankly, pretty tiresome. So let’s just hit the summary that Derek made for us:

Type I: None at the moment (that’s a tall order)

Type II: DIOSynvax ^[4], from a Cambridge startup working with CEPI.

Type III: Walter Reed’s SpFN ferritin-nanoparticle vaccine. ^[5] GBP511 ^[6] is coming along towards the clinic here, too.

Type IV: Gritstone Bio’s GRT-R910 ^[7], ImmunityBio’s hAd5 S+N. ^[8]

There’s more, but that’s a wide variety of vaccinations at various breadths with various technologies, all at different (early) stages. No idea what, if anything, will come of that.

Don’t expect super-rapid development like the Pfizer and Moderna vaccines, since those were emergency crash-priority projects.

The Weekend Conclusion

Beats me.

It’s all pretty early phase, and the stench of press releases lingers over most of it (with a couple notable exceptions).

While we can hope, I hope that isn’t false hope.

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Notes & References

1: D Lowe, “Are Pan-Coronavirus Vaccines Possible?”, In the Pipeline blog @ Science Translational Medicine, 2022-Apr-21. ↩

2: J Cui, F Li & Z-L Shi, “Origin and evolution of pathogenic coronaviruses”, Nat Rev Microbiol 17, 181-192, 2018-Dec-10. NB: This paper was published before the SARS-CoV2 driven COVID-19 pandemic, so it only includes the original SARS-CoV virus in the phylogeny. ↩

3: E Dolgin, “Pan-coronavirus vaccine pipeline takes form”, Nature Reviews Drug Discovery 21, 324-326, news section, 2022-Apr-19. DOI: 10.1038/d41573-022-00074-6. ↩

4: CEPI, “CEPI and DIOSynVax partner in quest to develop broadly protective Betacoronavirus vaccine”, CEPI News Releases, 2022-Mar-08. ↩

5: Precision Vaccinations Staff, “SpFN COVID-19 Vaccine”, Precision Vaccinations, 2022-Apr-22. ↩

6: AC Walls, “Elicitation of broadly protective sarbecovirus immunity by receptor-binding domain nanoparticle vaccines”, Cell, 2021-Sep-14. DOI: 10.1016/j.cell.2021.09.015. ↩

7: D Budwick, “Gritstone Announces Dosing of First Volunteer in Trial Evaluating Self-Amplifying mRNA as a COVID-19 Vaccine Booster and Immunogenicity Enhancer”, Gritstone Bio Press Releases, 2021-Sep-20. ↩

8: ImmunityBio, “Fighting a war on two fronts: ImmunityBio targets cancer and COVID-19”, Nature ‘advertisement feature’, undated. ↩