Derek Lowe’s commentary on drug discovery and the pharma industry. An editorially independent blog from the publishers of Science Translational Medicine. All content is Derek’s own, and he does not in any way speak for his employer.
The hype began building late last week around the Oxford vaccine results released today, and I will confess to wondering just what was going on. The British press has a history of going berserk over drug research – I wouldn’t care to count how many times Alzheimer’s “breakthroughs” have hit the headlines over there, and I figured this might be part of the problem. But now we have the numbers. So how are they?
Recall this this one is an adenovirus vector vaccine – a chimpanzee adenovirus (used because humans don’t have exposure and thus pre-existing immunity to it) has had its own genetic material stripped out and the genetic sequence for the coronavirus Spike protein added instead. There are four groups in this study: Group 1 had 88 participants who received either the ChAdOx vaccine or a commercial meningitis vaccine as a control and who were followed up on at Days 3, 7, 14, 28, and 56. These were the true “Phase I” part of the current work. Group 2 had 412 (also split 50/50) who were vaccinated and assessed for both antibody and T-cell counts. Group 3 (10 patients) all had the ChAdOx vaccine, and then a booster at Day 28. And Group 4 (567 patients, split 50/50) were only evaluated for antibodies. These latter groups are the Phase II trial, who are being evaluated for how many in each group actually contracted the coronavirus (data not available yet!) Everyone got the same dose: 5×10 to the tenth viral particles.
The adverse events are (as in the other vaccines that have reported so far) just what one would figure: pain and tenderness at the injection site, along with fatigue, muscle and joint pain, fever in some cases, etc. There were no severe events. Some participants got prophylactic paracetamol (acetaminophen), and this did indeed lower the side effects, as it should. I found it interesting that the second dose (in those ten patients who got one) did not seem to bring on a more robust reaction than the first (the paper’s Figure 2).
OK, antibodies: overall antibody titers hit their peak at Day 28 and had declined a bit at Day 56 (albeit with a rather wide spread in response in both sets of data – see the paper’s Figure 3 and note the log scale on the y axis). The ten patients who got the booster shot definitely saw raised antibody titers. As for neutralizing antibodies (the paper’s Figure 4), the booster-shot people did have a higher response than the single-dose cohort, an effect that’s most noticeable as you move to more stringent assays (in some of the others, they look nearly the same). But from what I can make of the actual neutralizing antibody titers, they all seem comparable (if not perhaps a bit lower) than those seen in the convalescent plasma control group. The activity for that comparison group does not seem to be reported in those other assays; it would be good to have that comparison. It’s also worth noting in those figures that there were a couple of patients who started out with high antibody titers to the coronavirus – as the paper notes, there was not time to check everyone as the trial was enrolling, so they picked up some people who are already had the infection.
As for T cells, the text of the paper says that induced T cell levels peaked at Day 14 and were maintained out to at least Day 56, with no real effect of a booster in that case. There are no actual data presented, and there’s nothing on CD4+ cells versus CD8+ ones.
These results, overall, are fine – but I think that they would have been more impressive had they come out before the Moderna and Pfizer mRNA ones. As it is, I have trouble reconciling the big buildup from the British media (and, I have to add, from the editorial staff at The Lancet) with what’s actually presented here. I’m very glad that I don’t have to pick which vaccine to get based on the limited data we have (there are no efficacy numbers to compare, to pick the biggest gap in our knowledge!) But if I were forced to make such a choice, right now I’d take the Pfizer/BioNTech candidate. But let’s see how everyone performs where it counts.