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Mix-and-match COVID-19 vaccine boosters are safe and prompt immune response, study finds
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Rajee Suri
Medical professional injecting syringe of vaccine into a patient's arm

An additional booster dose of any of the COVID-19 vaccines authorized for emergency use or approved by the U.S. Food and Drug Administration (FDA) was safe and boosted immune responses in people who had received a full regimen of any of these vaccines before.

The study, based on an analysis of preliminary clinical trial results, was published today in The New England Journal of Medicine.

The data are the first to be published from an ongoing Phase 1/2 trial sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

The findings of the investigation, led by the Infectious Diseases Clinical Research Consortium (IDCRC), first published in this preprint, resulted in recent recommendations by the FDA and Centers for Disease Control and Prevention (CDC) to allow mix-and-match of COVID-19 vaccine boosters.

Emory University was one of 10 institutions nationwide which participated in the study. The principal investigator (PI) of the study at Emory’s Hope Clinic and a professor in the School of Medicine, Srilatha Edupuganti, says the ability to use a different vaccine for boosting than the one originally used can potentially simplify vaccine booster administration. “I am pleased that we were able to do this study in a timely manner and obtain the data needed to guide the FDA and CDC’s decision about mixing and matching COVID-19 booster vaccines,” she says.

Expressing gratitude for the commitment of study participants, Christina Rostad, assistant professor in Emory’s School of Medicine and PI and study lead at the Emory Children’s Center,  says the findings indicate that booster vaccines can “enhance waning immunity and expand the breadth of immunity to SARS-CoV-2 variants of concern, including Omicron.”

“This study also shows that you don’t have to receive the same booster as your initial vaccine series to generate a strong immune response,” she says.

The study looked at findings from 458 adults who had been fully vaccinated with one of the three authorized COVID-19 vaccines – Moderna, Pfizer BioNTech, or Johnson & Johnson – at least 12 weeks prior to enrollment and who had no reported history of SARS-CoV-2 infection. At enrollment, a single booster dose was administered to each participant: 150 received Johnson & Johnson; 154 received Moderna; and 154 received Pfizer-BioNTech. Depending on which primary vaccine regimen a participant had received, the booster vaccine was either different (heterologous) or the same (homologous) as the original vaccine, and hence the term, “mix-and-match.”

Investigators measured responses that can help predict the level of immunity to SARS-CoV-2, including higher antibody levels and the creation of virus-specific T cells. Homologous and heterologous booster vaccinations were safe and immunogenic in adults who completed a primary COVID-19 vaccine regimen at least 12 weeks earlier. At 15 days after booster vaccination, serum antibody levels increased in all study groups, and leveled off by day 29. All combinations of primary and booster vaccine resulted in increased neutralizing antibody levels.

For each primary COVID-19 vaccine, mix-and-match boosters elicited similar or higher antibody responses as compared to getting the same vaccine. Increased levels of neutralizing antibodies have been found to correlate with protection against COVID-19. T-cell responses increased in most, and CD8+ T-cell levels were more durable and substantially boosted in the Johnson and Johnson vaccine recipients.

The IDCRC trial, which began enrollment in May 2021, is led by the study co-chairs, Robert L. Atmar, MD, of Baylor College of Medicine, Houston, TX, and Kirsten E. Lyke, MD, of the University of Maryland School of Medicine, Baltimore, MD.

NIAID grants supporting this research are UM1AI48372, UM1AI148373, UM1AI148450, UM1AI148452, UM1AI148573, UM1AI148574, UM1AI148575, UM1AI148576, UM1AI148684, UM1 AI148689 and with support from the NIAID Collaborative Influenza Vaccine Innovation Centers (CIVICs) contract 75N93019C00050.

About Infectious Disease Clinical Research Consortium (IDCRC)

The IDCRC, consisting of the Vaccine Treatment and Evaluation Units (VTEUs) and the IDCRC Leadership Group (under award number UM1AI148684), was formed in 2019 to support the planning and implementation of infectious diseases clinical research that efficiently addresses the scientific priorities of NIAID. The consortium directed by David S. Stephens, MD, of Emory University and Kathleen M. Neuzil, MD, at the University of Maryland Baltimore includes infectious diseases leaders and clinical researchers from Emory University, University of Maryland School of Medicine, Baylor College of Medicine, Cincinnati Children’s Medical Center and University of Cincinnati, FHI360, Fred Hutchinson Cancer Research Center, Johns Hopkins University, Kaiser Permanente Washington Health Research Institute, New York University, Saint Louis University, Vanderbilt University Medical Center, University of Alabama at Birmingham, University of Rochester, University of Washington, other affiliated sites and NIAID.

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