Several days after making headlines with a press release on the data, the Novavax Immunization Effort (NVAX) posted on medRxiv. This is the first look at the human data we have from an approach using recombinant coronavirus proteins (plus an adjuvant, in this case a proprietary natural saponin product). The protein itself is produced in the right Sf9 / baculovirus cell expression system, a workhorse over the years for recombinant proteins. Glad to see this one, because we need as many different techniques as possible. So how does it work?
This was done in 131 adults, with two injections three weeks apart. It was either 5 micrograms or 25 micrograms of protein, with and without the company’s proprietary adjuvant. As seen in some of the other trials, there were six patients in a ‘sentinal’ group who underwent the first observational dosing before the rest of the groups were vaccinated (five groups, 25 / group, with one. placebo cohort). The antigen itself is the full-length Spike protein, with the mutated furin protease site and two proline substitutions introduced to stabilize the conformation. This is pretty much the protein that the J&J vaccine (JNJ) causes cells to produce via its adenovirus vector, so in this case, it is simply injected directly.
The reactions to the vaccine itself appear to be good – the usual pain at the injection site and a few reports of mild transient fever. These were more visible in the adjuvant group, which basically tells you that the adjuvant is probably only doing its immunogenic action. Overall, there does not appear to be any clear signs of safety concern.
And indeed the adjuvant really helps a lot. On day 21 (before the second injection), antibody levels against Spike’s protein antigen were ten times higher in the adjuvant group compared to single injections. The response was also stronger after the second injection, and 14 days after this (day 35 total), antibody levels for the adjuvant groups were at least 100 times higher than those for the non-adjuvant groups. So that fixes that! Interestingly, the levels were quite similar for the 5 microgram and 25 microgram groups, which should also help with the overall manufacture of the vaccines.
The effect on neutralizing antibodies was even more striking – it’s an adjuvant or bust when measured this way (which is really the key number, anyway). After the second vaccination, the pre-print reports that neutralizing antibodies were four times higher than those seen in convalescent serum of coronavirus cases treated on an outpatient basis, and covering the same range as inpatient convalescent cases. 16 patients were randomly selected from the treatment groups to verify T cell response, and these showed CD4 + cells strongly biased in favor of Th1. We don’t know how long either response takes – this article covers up to two weeks after the second dose, but you can be sure those numbers are being collected.
It looks like solid results, and I’m happy this candidate is in human efficacy trials. This is something to emphasize – we all (naturally enough) try to do what we can based on phase I immunogenicity data and non-human-primate challenge experiments. But what matters is real human data in the field via phase II / III clinical trials. Right now we have several vaccines that seem to have a good chance of working (this is one of them). And we’re going to sort them out the only way they can be sorted.
Editor’s Note: The bullet points for this article were chosen by the editors of Seeking Alpha.