Why Does the AstraZeneca COVID-19 Vaccine’s Efficacy Vary?

AstraZeneca’s COVID-19 vaccine is up to 90% effective, the company said Monday in a press release, making it the third pharmaceutical firm to report promising vaccine news, following Pfizer and Moderna. AstraZeneca, which partnered with University of Oxford researchers to develop its two-dose vaccine, reported efficacy from two different dosing regimens; one led to 62% efficacy and another to 90%, with an average, the company says, of 70%.

The company’s vaccine was initially developed by Oxford scientists, who started with a disabled cold virus that commonly infects chimpanzees. It’s a more traditional approach than the strategy used by Moderna and Pfizer, both of which relied on the genetic mRNA code from SARS-CoV-2, the virus that causes COVID-19. The Oxford team used the cold virus as a molecular Trojan horse (technically known as a “vector”) to disguise the true payload: material from SARS-CoV-2, which triggers the human immune system into action. The chimp virus helps to deliver the coronavirus more efficiently without causing actual COVID-19.

Among people who received a half dose of the AstraZeneca vaccine, and then a full dose about a month later, about 90% were protected from symptomatic COVID-19 illness. Among those getting two full doses of vaccine a month apart, 62% were protected from getting sick. None of the people receiving either regimen were hospitalized or became severely ill. And the company said no serious side effects were reported—an important consideration since the trial was halted in early September after a participant developed an inflammatory reaction. The study resumed in the UK a week later, and in Brazil several weeks afterward when health officials determined the side effect was not related to the vaccine, but the US Food and Drug Administration (FDA) did not approve resuming the trial until late October.

The data, part of a scheduled efficacy review, are based on 131 cases of COVID-19 among both the vaccinated and placebo groups. But because the full set of data has not been published, vaccine experts—including regulators—are still trying to figure out why the different regimens led to different results. “The different levels of efficacy with two different dosing regimens is scientifically intriguing,” says Dr. Jessica Justman, associate professor of medicine in epidemiology at Columbia Mailman School of Public Health and senior technical director of ICAP at Columbia, a global public health services group.

One possible explanation relates to the vaccine’s design. Because it relies on a weakened cold virus to deliver the COVID-19 viral material, recipients’ immune systems may actually be mounting a response to the cold virus rather than the coronavirus. Halving the first dose helps to dampen this immune response to the cold virus, possibly increasing the response to the coronavirus.

“We know with other [cold] virus vectors you do get immunity to the vector,”…