We have more data on the J&J/Janssen coronavirus vaccine, which those keeping score at home will remember is an adenovirus vector candidate. It uses an obscure member of that virus family (Ad26) that very few people have ever been exposed to, as opposed to the ones where significant parts of the population might have pre-existing antibodies to the vaccine vector itself. And it’s also significant because it’s the only vaccine that’s in late-stage efficacy trials where the dosing schedule is a single shot, as opposed to a two-dose booster regimen.
So how does it look? The results in this preprint cover several trial arms – groups of volunteers 18 to 55 years old (Cohorts 1a and 1b) and those >65 years old (Cohort 3), at two different viral particle loading levels (one twice as high as the other). All of this was done in late July and early August. The first thing to note is that safety looks fine, so far – the usual site-of-injection reactions, along with some fever and fatigue in some patients. This was more noticeable in the younger cohort, which fits with the general trend of older patients having less reactive immune systems in general. Safety for all of the vaccine candidates is going to have to be established in the larger Phase III trials, of course, but I don’t think there’s anything to be worried about in these Phase I/II data (which feature about 400 people in each group). One patient was hospitalized overnight with fever, which was later determined to be vaccine-related, so we’ll keep an eye out for that.
As for antibody responses, it looks like one shot of the higher vaccine load leads to a higher response than the half-sized lower one in the 18-55 year old groups, but both of the doses showed strong seroconversion by day 29. And even that difference was not as apparent when neutralizing antibodies were measured, as opposed to total antibody titers: the two doses really look basically identical in that measurement. This paper has data from only 15 patients in the 65-and-over cohort, unfortunately, so it’s going to be risky to draw conclusions. But from what I can see (Figure 2 in the paper), their responses are broadly similar, but there’s a possible trend towards the higher dose actually being less effective. I’m not going to get worked up about that until more than fifteen data points are available, though.
What I do wonder about, though, is the comparison to convalescent plasma antibody levels. The total antibody measurements look quite similar, but frankly, the neutralizing antibody titers look higher in the recovered-patient panel than they do for the vaccinated cohorts (Figure 2B). I’m not sure what to make of this. The paper notes, however, that the 95% confidence interval overlaps between the convalescent plasma comparison group and both vaccine groups, though, and also goes out of its way to mention that some of the vaccine patients hit the upper limit of the assay and are being re-analyzed, which will raise the numbers there. So you can tell that the authors most certainly noticed this trend in the numbers, a feeling that’s reinforced by the discussion section of the paper where the lack of standardization of convalescent plasma samples is noted in detail.
We do have T-cell data, however, and this shows that both CD4+ and CD8+ cells are produced, with the former very strongly biased towards the Th1 response. The earlier experience with SARS and MERS suggest that a Th2-biased response runs the risk for vaccine-associated enhanced respiratory disease, so this is likely a good profile.
This is necessarily an incomplete report. As mentioned, there are only fifteen data points in the older patients, and there are several assays mentioned (such as a pseudovirus neutralization one) whose results will only be available later. But overall, this single-dose vaccination continues to look pretty strong, although we find ourselves right back where we always land at this point: waiting for efficacy data. Antibody titers and T-cell counts are useful and necessary (if they weren’t where they are in this report, that would be trouble). But they’re not enough, and we don’t know what “enough” might be. That can’t be overemphasized – at this point, all of these earlier-stage data are increasingly in the “Great, great, that’s nice” category (well, when they work!) because they’re going to be totally overshadowed by the real-world protection data that we’re all waiting on.