I know that it’s been a run of vaccine posts around here, but the numbers just keep on coming. Today we have two more papers to look at, both published in The Lancet. –
The first is from the SinoVac inactivated virus effort (the CoronaVac vaccine). In this one, the virus is grown in Vero cell culture, harvested, and inactivated by treatment with beta-propiolactone. As mentioned in previous vaccine roundups, this is an older technique. Its advantages are that it’s a well-worked-out technology, but the disadvantages are that it’s also known to produce less active vaccines overall.
This paper is just safety, tolerability, and immunogenicity in the human trials; we don’t have actual efficacy data yet (although you’d figure that’s coming soon). And overall, it looks like the vaccine works, but not as strongly as some of the other data we’ve seen. This trial looked at 3-microgram and 6-microgram doses of the inactivated virus preparation (with an aluminum hydroxide adjuvant), in two rounds spaced either 14 or 28 days apart. The antibody response after the second dose was not impressive in the first trial – even after the second dose, only about 80% of the patients seroconverted with neutralizing antibodies. But the Phase II trial was more like it, with 95% to 99% of people seroconverting. The paper says:
The immune response in the phase 2 study was substantially higher than in the phase 1 study, which might be due to the difference in preparation process of vaccine batches used in phase 1 and 2 resulting in a higher proportion of intact spike protein on the purified inactivated SARS-CoV-2 virions in the vaccine used in phase 2 than that used in phase 1.
That’s interesting, to have changed things in mid-stream like that, but perhaps it was the unimpressive results the first time through that prompted it? But even with that change, the antibody titers seen after the second dose were (in all patients) lower than those seen in a panel of 117 recovered coronavirus patients. There is no detailed T-cell data, but the paper does mention that ELISpot assays “provided no clear evidence that the vaccine induced T-cell responses“. So that’s the big question here: is all this enough? It might be, but it might not (or not be enough compared to other vaccine options). We’re not going to know until we see actual efficacy numbers from the trials that are going on in Brazil, Indonesia, and Turkey. The Brazilian trial, you will have heard, has been turbulent and was suddenly halted last week on orders from Brazil’s turbulent president. What this will do to the statistics or timeliness of the overall results is not clear.
The other paper is from the AstraZeneca/Oxford adenovirus vector effort. It’s a look at safety and immunogenicity in a wider spectrum of patients than has been reported so far, and the main news from it is that older patients appear to respond very similarly to the younger ones, both in antibody titers and T cells. What’s more, the vaccine actually appears to be better tolerated in the older patients (both in local reactions at the site of injection and systemically). So that’s good news. The actual antibody and T-cell numbers are similar to the earlier report, and would appear to be what you’d need for an effective vaccine, but we’ll again have to wait for the real numbers. Those shouldn’t be long in coming – BioCentury has a graphic of the current advanced-trial vaccine landscape here, and they (and others) expect to hear from both the AZ/Oxford team and J&J’s single-dose trial in December. At that point, we will have a completely unprecedented look at the landscape: large nearly-simultaneous data sets for two different mRNA vaccines and two different adenovirus vector ones, all directed to the same pathogen, and neither technology ever having advanced into humans like this. Let’s hope we never see the like again, because you would only do it this way when your back is against the wall.