Understand how we got here — and how to move forward.


June 29, 2021

3 new studies shed light on big questions about Covid-19 vaccines

Daily Briefing

    Three new studies released Monday are shedding new light on key questions about Covid-19 vaccines, including how long the immune response to vaccination lasts, whether it's effective to "mix and match" doses of different manufacturers' vaccines, and whether a third vaccine shot can effectively function as a booster.

    Is America's coronavirus future 'good,' 'bad,' or 'ugly'? It's all three.

    How long does the post-vaccine immune response last?

    In one study, published in Nature, researchers examined 14 people to determine how vaccines affected structures called germinal centers, which form in lymph nodes after a person contracts Covid-19 or is vaccinated against it.

    Ali Ellebedy, an immunologist at Washington University in St. Louis and lead author on the study, described the germinal centers as "boot camps for immune cells."

    "Germinal centers are the key to a persistent, protective immune response," Ellebedy explained. "Germinal centers are where our immune memories are formed. And the longer we have a germinal center, the stronger and more durable our immunity will be because there's a fierce selection process happening there, and only the best immune cells survive."

    The study found that 15 weeks after vaccination, the germinal centers were still active, and the immune cells were still learning to recognize a range of viral genetic sequences. According to researchers, this robust, ongoing immune response suggests that the immune system is likely developing the tools it needs to defeat variants of the coronavirus.

    People who had recovered from Covid-19 and later received a vaccine displayed an especially powerful immune response, the study found.

    The study looked only at mRNA vaccines, such as those developed by Pfizer-BioNTech and Moderna. It did not evaluate the vaccines developed by Johnson & Johnson or AstraZeneca, which Ellebedy believes won't drive as durable an immune response as mRNA vaccines.

    Is it effective to 'mix and match' vaccines?

    Another study, published in preprint form by The Lancet, examined how mixing different types of vaccines affected the immune response to the coronavirus.

    For the study, called Com-COV, researchers gave 830 volunteers one of four combinations of vaccines:

    • Two doses of the Pfizer-BioNTech vaccine;
    • Two doses of the AstraZeneca vaccine;
    • One dose of the AstraZeneca vaccine followed by a dose of the Pfizer-BioNTech vaccine; or
    • One dose of the Pfizer-BioNTech vaccine followed by a dose of the AstraZeneca vaccine.

    By and large, the researchers found that the Pfizer-BioNTech drove stronger immune responses than the AstraZeneca vaccine. For instance, participants who received two doses of the Pfizer-BioNTech vaccine developed antibody levels 10 times greater than those who received two doses of the AstraZeneca vaccine.

    But adding a single dose of the Pfizer-BioNTech vaccine to an AstraZeneca dose appeared to drive a notably strong immune response.

    For instance, those who received the Pfizer-BioNTech vaccine followed by the AstraZeneca vaccine saw antibody levels five times greater than those who received two doses of the AstraZeneca vaccine. And strikingly, those who received the AstraZeneca vaccine followed by the Pfizer-BioNTech vaccine saw antibody levels roughly equal to those who received two doses of the Pfizer-BioNTech vaccine.

    The researchers also found that mixing vaccines produced higher levels of immune cells prepared to attack the coronavirus than receiving two doses of the same vaccine. Matthew Snape, a vaccine expert at the University of Oxford and an author on the study, said he's unsure why mixing produced that result. "It's very intriguing, let's say that much," he said.

    The researchers did find, however, that those who received doses of different vaccines reported more chills, headaches, and muscle pain than those who received two doses of the same vaccine. These side effects didn't last long, however.

    Snape said the results suggest administering the vaccines in any order will work. "Any of these schedules, I think could be argued, would be expected to be effective," he said.

    Can a third shot function as a booster?

    Another study, also published as a preprint study with The Lancet, looked at how a third dose of AstraZeneca's vaccine affected immune response.

    For the study, researchers gave 90 volunteers a third dose of AstraZeneca's vaccine roughly 30 weeks after they received their second dose. Their antibody levels then rose to higher levels than they'd reached a month after a second dose, suggesting a third dose provides extra protection against the coronavirus.

    The study also looked at 30 volunteers who had received their second dose of AstraZeneca's vaccine on a delayed schedule. The researchers found that the second dose can be delayed for as much as 45 weeks from the first dose and still produce an enhanced immune response.

    "There had been some concerns that we would not be able to use this vaccine in a booster vaccination regime, and that's certainly not what the data is suggesting," Teresa Lambe, from Oxford's Jenner Institute, said.

    "We do have to be in a position where we could boost, if it turned out that was necessary," Andrew Pollard, a vaccine researcher at Oxford, said. "I think we have encouraging data in this preprint to show that boosters could be used and would be effective at boosting the immune response." (Mandavilli et al., New York Times, 6/28; Zimmer, New York Times, 6/28; Smout, Reuters, 6/28; Adams, Becker's Hospital Review, 6/28; Sullivan, The Hill, 6/28; Canadian Press/Modern Healthcare, 6/28)

    Is America's coronavirus future 'good,' 'bad,' or 'ugly'? It's all three.

    looking aheadSince February, Advisory Board's Brandi Greenberg has been tracking three ways the U.S. coronavirus epidemic could end: the "good," the "bad," and the "ugly." But new data, she says, has forced her to revise her expectations about what Covid-19's future will look like—for America and for the world. 

    Read the latest take

    Have a Question?


    Ask our experts a question on any topic in health care by visiting our member portal, AskAdvisory.