Thread by @PeterKolchinsky

New data from Novavax vaccine just showed that UK & esp South African variants are more problematic in real world than lab experiments suggested. Implications are profound for 2021 and beyond. nytimes.com/2021/01/28/hea…

Vaccine worked well to stop original strain (96%), like mRNA vaccines, but less effective for new strains (86% for UK strain, 60% protective against South African strain). My guess is that if mRNA vaccines were tested now in a clinical trial in South Africa...

...they would show similar reduction in effectiveness. Bottom line, new SA strain has evolved SOME (not total) resistance to current vaccines. Current vaccines still help blunt severity, so worth getting even in South Africa.

But this means that even if everyone got the current vaccine and stopped social distancing, then new variant could end up causing more harm than SARS2 does now. That’s the big deal. New variant is extending the pandemic until we have new vaccines.

Everyone who got first vaccine will want a booster shot against the new SA variant. Ultimately, we need combo vaccines that immunize against both original and SA strains.

Novavax is responding logically, by advancing a combo vaccine into clinic that will include South African spike antigen that they say will enter trials in 2Q21. I assume it takes 3 months more for early evidence of effectiveness against SA strain, so summer maybe.

mRNA companies are also working on vaccine against new strain. They will probably be able to roll out boosters soonest of any companies for people who already got vaccines & just need new booster. But will be interesting to see how they develop a combo vaccine for first timers.

That’s because mRNA vaccines are limited by tolerability in how much mRNA you can jam into a dose. The more mRNA you give, the more painful, more fever, etc. It’s easier to double and triple up the antigens for a more conventional protein-based vaccine.

That’s b/c protein vaccine uses a separate immune stimulating adjuvant. Can give 2, 3, 4 proteins covering unique strains while keeping dose of adjuvant the same, so immune system isn’t over-stimulated. But mRNA is its own adjuvant; so more strains means more immune stimulation.

What about JNJ & AZ adenoviral vaccines? We’ll likely see next week how effective JNJ’s is against original & new strains but odds are it will be less effective against new strain. Since Ad vaccines probably can’t be redosed (immune system learns to recognize & reject vector)...

...those vaccines won’t be good for keeping up with new strains. So I don’t see adenoviral vaccines as useful for the long run management of SARS2 due to weak efficacy and challenge with redosing.

If SA variant is last variant we need to defeat (unlikely), we’ll be able to do so w/ mRNA & protein vaccines. But if new variants keep emerging, we may need to expand vaccines to more antigens than mRNA seems to tolerably accommodate, putting all focus on protein-based vaccines.

So sadly I now think 2021 is going to be rough & we’ll be talking about progress of vaccines against new strains. If we see data by MY21 that new vaccines against new strain work, then hopefully FDA allows faster approval of subsequent upgrades in response to yet new strains.

Key is to keep investing in expansion of manufacturing capacities of the vaccines that are most likely to allow us to expand them to cover more strains and to redose with boosters. That means investing in massive scale-up of protein-based vaccines.

And it also means that we’ll need to continue conducting global surveillance for emergence of new variants to give vaccine companies a head start to update their vaccines. That means more sequencing of positives samples, particularly in regions with escalating infections.

These data are painful for what they mean for the world. This virus is a tough opponent. Just shows how critical vaccines, therapeutics, & diagnostics remain to fighting this virus. It’s going to be with us forever, not just killing but causing all kinds of disabilities.

We’ll be updating our map and doing some more analysis. I’m sure our team will be having an active debate on our next RA TV episode. check out racap.com/covid-19.

Update: like AZ’s, JNJ vaccine less effective on original strain than other vaccines (insight into Ad vector) &, as w/Novavax, less effective against new SA strain (insight into virus). Worth taking b/c blunts severity of disease regardless of strain. nbcnews.com/health/health-…

So we have to 1) roll out existing vaccines asap, 2) people should take them, 3) remain cautious (esp around unvaccinated) b/c SA strain can spread despite vaccine & mod disease isn’t fun, & 4) upgrade vaccines to cover SA strain, for which adjuvanted vaccines are well suited.