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October 14, 2021

What new research reveals about 'mixing and matching' Covid-19 vaccines

Daily Briefing

    A second dose of Johnson & Johnson's (J&J) Covid-19 vaccine would likely increase protection for recipients, according to a new FDA report—but separate research suggests that a booster dose of an mRNA vaccine could be even more beneficial.

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    What FDA's staff found about a J&J booster shot

    In an FDA staff report released Wednesday, the agency's staff said a second dose of J&J's Covid-19 vaccine likely would benefit recipients of an initial dose. They noted, however, that data on the company's booster doses is limited.

    According to the FDA report, a large study sponsored by the company found that two doses of J&J's vaccine administered two months apart were 75% effective against moderate-to-severe Covid-19.

    The report noted, "Although not independently confirmed by FDA from datasets, summaries of the data suggest there may be a benefit in a second dose administered approximately two months after the primary dose."

    The agency added that there was insufficient data to determine the efficacy of booster doses against the delta variant and in adults ages 60 and up.

    In addition, the FDA staff report said that while a single dose of J&J's vaccine "still affords protection against severe Covid-19 disease and death in the United States," its highest estimated levels of protection, including against severe Covid-19, were "consistently less than the highest effectiveness estimates" for the Moderna and Pfizer-BioNTech's mRNA vaccines.

    Separate research sees promise in 'mixing and matching' vaccines

    While the FDA staff report looked only at the possibility of giving J&J vaccine recipients a second dose of the same vaccine, separate research released Wednesday explored the possibility of "mixing and matching" the three vaccines authorized in the United States.

    For the preprint study from NIH, researchers organized 458 participants into nine groups of roughly 50 people each. Each group received one of the three authorized Covid-19 vaccines, followed by a booster dose four to six months after primary immunization. In three groups, participants received the same vaccine for their booster, while in six groups, participants received a different brand.

    Researchers measured participants' antibody levels two and four weeks after receiving a booster dose. Boosters of all three vaccines generated a strong immune response, with the mRNA vaccines having a higher increase in antibodies compared to J&J's vaccine.

    In particular, researchers found participants who initially received the J&J vaccine experienced a significantly higher increase in antibody levels after receiving an mRNA booster compared to a J&J booster. Specifically, a J&J dose followed by a Moderna booster led to a 76-fold increase in antibody levels, and a J&J dose followed by a Pfizer-BioNTech booster led to a 35-fold increase. In comparison, a second J&J dose only led to a four-fold increase in antibody levels.

    The researchers also noted differences in immune responses of participants who initially received the Moderna or Pfizer-BioNTech vaccines and then a different mRNA booster. The differences, however, were likely too small to significantly affect protection, NPR reports.

    According to the Times, the authors cautioned that the results of the study are not conclusive, citing its small sample size and the fact that they did not follow participants long enough to identify rare side effects.

    Scott Hensley, an immunologist at the University of Pennsylvania who was not involved in the NIH study, said he found the results compelling, but noted the study only measured antibody levels, which alone may not be sufficient to measure immunity, the Times reports.

    "At the end of the day, folks having the [J&J vaccine] should probably get an mRNA booster," Hensley said. "It's just a matter of, how much data does the [FDA] need before making that recommendation?"

    Separately, Leana Wen, an emergency physician and public health professor at George Washington University, said the study's results suggest mixing and matching vaccines for booster doses is safe and effective.

    "I hope that the FDA and CDC will consider these results in their deliberations and allow, in particular, for recipients of the Johnson & Johnson vaccine to receive an mRNA second dose," Wen said.

    According to the Times, FDA's Vaccines and Related Biological Products Advisory Committee is scheduled to vote on Friday whether the agency should authorize booster doses of J&J's vaccine. The committee will also discuss a strategy for mixing and matching vaccines, although a vote will not be taken at the time. (Stein, NPR, 10/13; Gardner/Owermohle, Politico, 10/13; Weixel, The Hill, 10/13 [1]; Zimmer/Weiland, New York Times, 10/13 [1]; Weise, USA Today, 10/13; Walker, MedPage Today, 10/13; Weixel, The Hill, 10/13 [2]; Zimmer/Weiland, New York Times, 10/13 [2]; Loftus/Schwartz, Wall Street Journal, 10/13)

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