When we last heard of the Pfizer (PFE) / BioNTech (BNTX) vaccine program, they had chosen a different candidate than the one they had already published on (BNT162b1). On Thursday, they released more details about the actual candidate, BNT162b2. And it seems pretty clear why they went with it.
This preprint describes a head-to-head study (NCT04368728) between their two candidates, in a fairly broad trial with 13 different treatment groups, varying from the age of the volunteers (18-55 or 65-85) and the vaccine dose (10, 20, or 30 micrograms, each in two doses 21 days apart, one group receiving a single shot of 100 micrograms). Each group had 12 people dosed with a vaccine candidate and 3 placebo controls.
Overall, the “b2” vaccine produced fewer reactions to injection, and milder systemic reactions such as fever, body aches, and so on. Older patients were most likely to have less response than younger patients, with both candidates. This is something to keep in mind – the other day I was wondering if the mild reactions to Sinopharm’s invasive virus vaccine (SHTDF) might indicate that it’s less of a reaction, but that’s clearly not always the case.
The antibody response in the two vaccines was quite similar, and they both showed the same trends (e.g., lower neutralizing anti-antibody response in the elderly patients, one-third to one-half, so there will be something to pay attention to if we obtain data on effectiveness). The booster shot was absolutely necessary – antibody titers were much better after the second injection. And although the 20 microgram dose was definitely better than the 10, the 30 microgram dose was slightly better in some groups, but not in others. However, Phase III will be two doses of 30 micrograms, as it also had no less safety signals.
The difference between the two candidates is that the b1 vaccine encodes the RBD of the Spike domain, presented as a trimmer, while the b2 vaccine is the full-length Spike with a few mutations to make it more stable. The b1 therefore has more real RNA molecules in it than the b2, but the formulation of the lipid nanoparticle is the same. The paper notes that it is not clear why the candidate for b2 has significantly fewer side effects – the number of RNAs could be part of it, but these effects are also known to depend on the particular RNA sequences that are involved, so who knows? The authors also reported that they expected a wider variety of T-cell responses from the full-length antibody in the b2 vaccine, but that this study did not include T-cell characterization. Pfizer’s own comments lead one to believe that this is what they are looking for, but was that based on data rather than expectations? Anyway, at least I didn’t go down without explaining myself first.
But what I most look forward to is seeing how all these Phase I profiles translate to the real world of protection against the coronavirus. We will soon learn more about immunological correlations than we have ever learned for one pathogen before. There are now so many different platforms in test subjects, each with their differences, and we’ll be getting fast successive stacks of data from threads of tens of thousands of people around the world. No one would ever have set up such a gigantic experimental landscape under non-emergency conditions; from the clinical perspective, it is an unusual immunological Woodstock.
And we’ll have to prepare for that. There are several believable outcomes (good, bad, and just mixed) that I do not think the general public has responded to, and that will be the subject of an upcoming post!
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