Receiving COVID-19 Booster Close to Time of Primary Vaccination Lowers Immune Response


Antibodies from an original COVID-19 vaccination may treat the mRNA booster vaccine as a virus that needs to be cleared.

Increasing the time between COVID-19 vaccinations appears to be better for stimulating an immune response, according to a study conducted by Northwestern Medicine and published in Cell Reports. This information may help in efforts to guide future vaccination regimens, according to the study authors.

“We showed in prior studies—as did other labs—that the longer the interval between vaccinations, the better the response. It’s better to wait 6 months than 2 weeks before you boost, but the reasons for this were not clear,” said study author Pablo Penaloza-MacMaster, assistant professor of microbiology-immunology at Northwestern University Feinberg School of Medicine, in a press release.

When received in proximity, the antibodies from the first vaccine can “hurt” booster shots, Penaloza-MacMaster explained. He noted that the antibodies think that the booster vaccine is a virus and “mop up” the booster before it can activate an immune response.

Investigators observed this in a recent study conducted on mice and humans. During the human portion of the study, investigators looked at the antibody levels of 85 people who received the Moderna or Pfizer-BioNTech COVID-19 vaccine. They found an association between lower antibody levels prior to boosting with a greater increase in antibody levels after booster vaccination.

“This suggests that pre-existing antibodies induced by prior vaccinations may negatively affect the level of responses induced by mRNA booster vaccines,” Penaloza-MacMaster said in the press release.

The Northwestern team also looked at the antibody levels of mice in a similar fashion, finding that the antibody response of the first vaccine, “rapidly wipe[d] out the vaccine during a subsequent booster shot,” Penaloza-MacMaster said in the release.

The investigators hypothesize that the antibodies from the first vaccine were defending the body against foreign invaders in the booster versus competing against the antibodies and B cells of the newer vaccine. They also discovered that the updated Omicron vaccine is better than the original vaccines at clearing Omicron infection in mice when their immune system had not “seen” the original variant of COVID-19.

Penaloza-MacMaster is looking forward to learning more about how to make more efficacious booster vaccines, he said in the press release. Understanding how time is important to their mechanism can improve mRNA boosters.

The team will be conducting new studies that look at the effects of administering drugs that block antibody activity while giving people a booster, which could stop the original antibodies from attacking the new vaccine.

“It is important to clarify that having antibodies and getting boosted is a good thing, so anyone who is due their booster shot should do so. We don’t want people to think otherwise,” Penaloza-MacMaster said in the press release. “The study just pinpoints potential strategies by which next-generation vaccines could be tweaked to improve their efficacy, for example, by developing vaccines that bypass pre-existing antibodies.”


Northwestern University. Your first COVID-19 vaccination ‘hurts’ subsequent boosters. News Release. February 15, 2023. Accessed on February 16, 2023.

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