And now we have more data on the CanSino vaccine, another adenovirus vector (but this one using Ad5, a much more common one in the human population). Their initial Phase I data are discussed here. So what else do we know now?
Well, that one was open label and non-randomized, whereas this one is fully controlled. It also is much larger, and has a wider range of ages and should be more of a real-world look. There are two doses (5 x ten to the tenth, 129 patients, and 1 times ten to the eleventh viral particles, 253 patients, and a comparison to a placebo group of 126 patients as well). 52% of them had high pre-existing immunity to adenovirus-5, which has always been a concern with this effort.
There were no serious adverse events in either dosing group, and the events that did take place were exactly the sort of thing we’ve been seeing before – pain and soreness at the injection site, general fatigue and aches, mild fever. It doesn’t look like we’re going to get away from any of those, so we should all remind ourselves that it damn well beats getting the coronavirus.
Both doses produced similar titers of neutralizing antibodies, as it turns out, and these kicked in sometime between Day 14 and Day 28. But when you look at the half of the subjects who already had high levels of antibodies to the Ad5 vector, you find that their titers were 2 to 3 times lower than the ones who didn’t start out that way. The patients who were older than 55 also showed noticeably lower antibody response – still above placebo, true, but nowhere near as robust as the younger patients. Older patients were more likely to have the Ad5 antibodies, which is surely a good part of the reason for this. None of the data in the paper go out past 28 days, so we can’t say much of anything about whether there’s a dropoff in antibody titers.
Both doses of vaccine produced a similar T-cell response, and in that case there’s no real difference between the ones with higher pre-existing Ad5 antibodies and the lower ones. These data are only shown as a snapshot at Day 28. Only about 1% of the patients showed any T-cell response at the baseline pre-dosing, interestingly. Another thing to note: the age of the patients seemed to make no difference in the T-cell response, as opposed to what was seen with the antibody levels. There are no data on CD4+ versus CD8+ cells, unfortunately.
Overall, then, this is a useful but limited publication. It tells us more about the CanSino vaccine’s profile, but it also raises some worries about just what everyone was already worried about: the pre-existing Ad5 immune response. This should come as no surprise to anyone, and the paper states clearly that this is their biggest concern going forward. In the Chinese population, about 50% of the population is in that category – in India it’s 80%, and in the US around 30%. The question is what differences one might see in the Phase II efficacy readouts. Remember, giving a booster shot with one of these viral-vector agents is quite problematic – after the first dose, the number of your patients who have neutralizing antibodies to the vector is now 100%. One the other hand giving one shot instead of two is potentially a big advantage – but only if that one shot is enough. Yet again, we’re going to have to let this shake out in Phase II. Maybe it won’t make a difference, but. . .given these concerns, if I were a betting man – perish the thought – this vaccine is not where I would be putting my money just now.