AstraZeneca announced results today from an interim analysis of its COVID-19 vaccine candidate that indicate the vaccine is 70% effective on average, according to an ongoing Phase III trial in the U.K. and Brazil. The vaccine candidate is the first of the viral vector platform vaccines to demonstrate efficacy, using an adenovirus that commonly infects chimpanzees to express the SARS-CoV-2 Spike (S) protein. This vaccine was developed in partnership with Oxford University and its spin-off Vaccitech. Both Pfizer/BioNTech and Moderna recently released interim efficacy results for their vaccine candidates, both of which are based on mRNA strategies for delivering vaccine antigens.

According to AstraZeneca’s press release, the interim analysis conducted by an independent data and safety monitoring board was based on 131 COVID-19 cases that have occurred in the trial so far. Intriguingly, among a subset of volunteers (2,741) who received a half dose of the vaccine candidate followed a month later by a full dose, the interim efficacy was 90%. Whereas, the efficacy was 62% among volunteers who received a full dose of the vaccine candidate followed a month later by a second full dose. Based on these findings, the company announced it would seek approval from the Food and Drug Administration to also evaluate this half-dose regimen in its ongoing U.S. trial, which is currently only evaluating the two full-dose regimen. No serious adverse events, hospitalizations, or severe cases of COVID-19 disease were reported among vaccine recipients, according to AstraZeneca.

Clinical trials of this vaccine are also ongoing in Japan, Russia, South Africa, and Latin America, with a targeted enrollment of up to 60,000 volunteers worldwide.

HVP Editor Kristen Jill Abboud discussed these results and their interpretation with Wayne Koff, founding President and CEO of the Human Vaccines Project (HVP), in light of the two other recent reports of COVID-19 vaccine efficacy data. An edited version of the conversation appears below. This special issue also includes reactions from several experts in the field and a summary of AstraZeneca’s ongoing Phase III efficacy trial.

Here we are with another interim efficacy result, this time with efficacy that differs based on the dosing regimen. What are your thoughts on this? How does this compare to the previous vaccine data released for the mRNA candidates?

Again, this is really exciting to have another positive result from the AstraZeneca/Oxford vaccine, but we are still dealing with the same caveats, which is we don’t yet have the complete data regarding the breakdown in infections, the durability, or the efficacy in specific sub-populations. We eagerly await publications for all three of these vaccine candidates, which should happen relatively soon. We’re all anxious, as a field, to see the data in full and to be able to compare them.

It’s a little early to understand any difference in efficacy between the different vaccination regimens for the AstraZeneca candidate and there are all the other questions regarding all three of the vaccines for which interim efficacy data have been reported, including the durability of the immune responses. I’m not sure what the mechanism could be for the efficacy varying by dosing regimen, but I would say that this really points again to the fact that we don’t understand a lot of the basics about human immunology or the best strategies for inducing protective immunity. For example, it would be ideal if we had an understanding of whether there are early markers of vaccine durability, and this is something we hope to be able to evaluate in the future.

What are some of the key findings related to this vaccine candidate that differentiate it from some of the other platforms?

The typical cold-chain storage—just being able to keep the vaccine stable in a normal refrigerator instead of at freezing temperatures—is a real advantage for this vaccine and should make deployment and delivery more feasible around the world. This alone should facilitate access. In the press release, the company also alludes to the fact that this vaccine may have the potential to block infection and not just prevent disease or serious disease, but again, without seeing the full data, we just don’t know. It is impossible to parse any differences based on just the press release.

Given that this viral vector platform now seems to be effective as well, do you suspect that most or all of the COVID-19 vaccine candidates are going to work?

If you make high enough titers of neutralizing antibodies against this virus in non-human primate studies, it appears that vaccine will likely be effective, with the caveat of course that to date, the correlate of protection from clinical trials has not been defined. We will have to wait to see if there are any differences that emerge between the candidates as we have more follow up and collect longer-term data. It is important to remember that for all of the candidates, this is only preliminary data based on a small number of infections and we will learn a lot more as these trials continue. Still, it is great news that we could have multiple effective vaccines relatively soon to deploy to help get this pandemic under control.

Interview by Kristen Jill Abboud