In a new—yet to be peer-reviewed—study, the pharmaceutical company AstraZeneca and its partners at the University of Oxford report that their COVID-19 shot may not only protect against disease but also help to prevent spread of the SARS-CoV-2 virus. The news was heralded by policy makers desperate to see a vaccine that can curb spread of the disease, but scientists have been a bit more cautious. If confirmed, the results would represent a breakthrough in the COVID-19 vaccine race. So far, the shots authorized or approved around the world have shown strong protection against moderate to severe disease, but haven’t definitively proven that people who get vaccinated are less likely to spread the COVID-19 virus.
But the data, say some experts, is confusing, so it’s hard to adequately evaluate the company’s claim that the shot can actually slow the spread of COVID-19 or not.
In the study, published on the Lancet pre-print server (which means the results have not been peer-reviewed, a gold standard for ensuring the scientific rigor of the findings) AstraZeneca and Oxford scientists report that two doses of their vaccine was overall 66.7% effective in protecting against COVID-19 disease. As part of its analysis, the research team also collected nasal swabs from vaccinated and unvaccinated study volunteers in the U.K. every week and tested them for the virus. The scientists found that positive tests were about 50% lower among people who got two doses of the vaccine compared to those who weren’t vaccinated. Because people who do not test positive are less likely to spread the virus, the researchers extrapolated from those data that the AstraZeneca shot can lower transmission of the COVID-19 virus.
However, that may be a bit of a stretch, says Dr. Carlos del Rio, executive associate dean of Emory School of Medicine. “It’s a leap of science that I think still needs to be proven,” he says. “What they show is that there was [either] decreased viral shedding or decreased detection of virus,” However, they do not actually show that transmission was decreased. “We can say less transmission is a possibility but the data on that needs to come out,” says Del Rio. “We want to state the facts and don’t want to over state the facts.”
That concern was echoed by health officials in Switzerland who decided this week to reject the AstraZeneca shot. “The data available and evaluated to date are not yet sufficient for approval,” the country’s regulatory body, SwissMedic, said on Feb. 3. Part of the concern has to do with the fact that the AstraZeneca study underwent a number of changes after the Phase 3 trial was begun, a fact that, some infectious disease experts say, makes it difficult to interpret the results. For a clinical trial as crucial as this one, modifying the setup once it’s underway is similar to changing the rules in the middle of a game. The study originally set out to investigate a single dose of vaccine, but was changed to two doses when concurrently conducted early studies showed that two set doses of the vaccine produced a stronger immune response.
Further, because of what AstraZeneca said were mistakes in measuring doses, some people in the study in the U.K. received a half dose for their first shot and a full dose for the second one. People also got different placebos—some got a benign meningococcal solution and some a saline solution. That could mean nothing, but it is also unusual to have two different placebos, since that has the potential to introduce confounders into the study. And because of limited supplies, some study participants had to wait more than the three to four weeks originally planned between their doses—while others, when told they couldn’t come back for their second dose at the time they expected, chose to simply not get their second shot entirely.
“Frankly the way they did these trials was really confusing,” says Dr. Paul Offit, director of the vaccine education center at Children’s Hospital of Philadelphia and a member of the U.S. Food and Drug Administration’s advisory committee that reviews vaccines for authorization or approval. “This is the stuff you figure out in Phase 1; you don’t fool around in Phase 3 and see what works.”
Here’s what the researchers report: After getting a single shot, 76% of participants were protected against disease for up to three months afterwards. From there, their levels of antibodies generated against the virus—which scientists believe are important to protect against disease—began to drop. Those results suggest that while two doses of the AstraZeneca vaccine are preferable, a single dose could still be useful—for about three months—in controlling COVID-19. That might be especially useful information to act on if vaccines are in short supply. Still, says Dr. Annie Luetkemeyer, professor of medicine at University of California, San Francisco who is leading one of the ongoing U.S. trials of the AstraZeneca vaccine, “These results show that a single dose is good enough for the first 90 days but we see that signal of efficacy drop after 90 days, and we see the immune response in terms of a stronger antibody response after the second dose. In combination, those two factors to me strongly suggest that a second dose should still be given.”
The new study also shows that if people are getting two shots, spacing them apart for up to three months could increase their level of protection. For those who got their second shot 12 or more weeks after the first, the vaccine was 82.4% effective in protecting against COVID-19 disease; among those who got their second shot less than six weeks after the first, the efficacy was 54.9%.
That led health officials in the U.K. in early Jan. to change the dosing regimen for both the Pfizer-BioNTech vaccine, the first to be authorized in the U.K., and the AstraZeneca-Oxford shot, so the second shot is given up to three months after the first. That decision was made as the slow rollout of the vaccines led to too few people getting vaccinated even as a new mutant strain started to dominate infections in the region. These latest data seem to support that decision, at least in part, and British health secretary Matt Hancock tweeted on Feb. 2 that the AstraZeneca findings were “absolutely superb.”
The AstraZeneca vaccine is not yet authorized in the U.S.; late-stage studies of the shot in the country are ongoing, and for now, U.S. health officials are adopting a wait-and-see approach about whether the results should signal a shift toward a longer time window between shots, or even a single shot strategy. At the White House’s regular COVID-19 briefing on Feb. 3, Dr. Anthony Fauci, the chief medical advisor to the president and director of the National Institute for Allergy and Infectious Diseases, said, “We respect that the U.K. scientists and health officials are going by their data and letting their own data dictate their policy,” he said. “We are going very much by the data and science that emanated out of the very large clinical trials—the Moderna trial of 30,000 people, and the Pfizer-BioNTech trial of 44,000 people—which indicated that the maximum response given with a prime [shot] followed by a boost [shot] came at 21 days with the Pfizer vaccine and 28 days with the Modera vaccine. We feel strongly that we will go by the science, which dictated for us the optimal way to get 94% to 95% response.”
Moderna’s and PfizerBioNTech’s vaccines are both 94% to 95% effective in protecting against COVID-19 disease after two shots. On Jan. 29, Johnson & Johnson’s Janssen group, the only vaccine maker testing a single-dose strategy, reported that its shot was 66% effective in protecting against COVID-19 disease after one dose.
As data from different vaccines start to pile up, it’s tempting to compare shots by their effectiveness, but that’s not always a useful exercise. The vaccines are made using different technologies that each have their own pros and cons, and while the U.S.-based studies were conducted using a uniform design and monitoring system, studies like the current one from AstraZeneca, conducted out of the U.K., used a different one. Del Rio says it’s likely that the results from the ongoing U.S. study, which scientists are analyzing now, and not the U.K.-based trial, may form the foundation for any request for authorization in the U.S.
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Contributor: Alice Park