• Robert L Atmar, Kirsten E Lyke, Meagan E Deming, Lisa A Jackson, Angela R Branche, Hana M El Sahly, Christina A Rostad, Judith M Martin, Christine Johnston, Richard E Rupp, Mark J Mulligan, Rebecca C Brady, Robert W Frenck, Martín Bäcker, Angelica C Kottkamp, Tara M Babu, Kumaravel Rajakumar, Srilatha Edupuganti, David Dobrzynski, Rhea N Coler, Christine M Posavad, Janet I Archer, Sonja Crandon, Seema U Nayak, Daniel Szydlo, Jillian A Zemanek, Clara P Dominguez Islas, Elizabeth R Brown, Mehul S Suthar, M Juliana McElrath, Adrian B McDermott, Sarah E O'Connell, David C Montefiori, Amanda Eaton, Kathleen M Neuzil, David S Stephens, Paul C Roberts, John H Beigel, and DMID 21-0012 Study Group.
• From the Departments of Medicine and Molecular Virology and Microbiology, Baylor College of Medicine, Houston (R.L.A., H.M.E.S.), and Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston (R.E.R.); the Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore (K.E.L., M.E.D., K.M.N.), and the Division of Microbiology and Infectious Diseases (S.C., S.U.N., P.C.R., J.H.B.) and the Vaccine Research Center (A.B.M., S.E.O.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda; Kaiser Permanente Washington Health Research Institute (L.A.J.), the Departments of Medicine (C.J., T.M.B., M.J. McElrath) and Laboratory Medicine and Pathology (C.J., C.M.P.), University of Washington, the Vaccine and Infectious Disease Division (C.J., C.M.P., C.P.D.I., E.R.B., M.J. McElrath) and the Statistical Center for HIV/AIDS Research and Prevention (D.S., J.A.Z.), Fred Hutchinson Cancer Research Center, and Seattle Children's Research Institute (R.N.C.) and the Department of Pediatrics (R.N.C.), University of Washington School of Medicine, Seattle; the Department of Medicine, Division of Infectious Diseases, University of Rochester, Rochester (A.R.B., D.D.), NYU Langone Vaccine Center and Division of Infectious Diseases and Immunology, Department of Medicine, NYU Grossman School of Medicine, New York (M.J. Mulligan, A.C.K.), and NYU Langone Hospital-Long Island Vaccine Center Research Clinic and the Division of Infectious Disease, Department of Medicine, NYU Long Island School of Medicine, Mineola (M.B.) - all in New York; the Departments of Pediatrics (C.A.R.), Microbiology and Immunology (M.S.S.), and Medicine (S.E., D.S.S.), the Center for Childhood Infections and Vaccines (C.A.R.), Hope Clinic of Emory Vaccine Center (S.E.), Emory Vaccine Center, and Yerkes National Primate Research Center (M.S.S.), Emory University School of Medicine, Emory University, and Children's Healthcare of Atlanta (C.A.R.) - all in Atlanta; the Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh (J.M.M., K.R.); Cincinnati Children's Hospital Medical Center, Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati (R.C.B., R.W.F.); and FHI 360 (formerly Family Health International) (J.I.A.) and Duke Human Vaccine Institute (D.C.M.) and the Department of Surgery (D.C.M., A.E.), Duke University Medical Center, Durham, NC.
• N. Engl. J. Med. 2022 Mar 17; 386 (11): 1046-1057.

BackgroundAlthough the three vaccines against coronavirus disease 2019 (Covid-19) that have received emergency use authorization in the United States are highly effective, breakthrough infections are occurring. Data are needed on the serial use of homologous boosters (same as the primary vaccine) and heterologous boosters (different from the primary vaccine) in fully vaccinated recipients.MethodsIn this phase 1-2, open-label clinical trial conducted at 10 sites in the United States, adults who had completed a Covid-19 vaccine regimen at least 12 weeks earlier and had no reported history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection received a booster injection with one of three vaccines: mRNA-1273 (Moderna) at a dose of 100 μg, Ad26.COV2.S (Johnson & Johnson-Janssen) at a dose of 5×1010 virus particles, or BNT162b2 (Pfizer-BioNTech) at a dose of 30 μg. The primary end points were safety, reactogenicity, and humoral immunogenicity on trial days 15 and 29.ResultsOf the 458 participants who were enrolled in the trial, 154 received mRNA-1273, 150 received Ad26.COV2.S, and 153 received BNT162b2 as booster vaccines; 1 participant did not receive the assigned vaccine. Reactogenicity was similar to that reported for the primary series. More than half the recipients reported having injection-site pain, malaise, headache, or myalgia. For all combinations, antibody neutralizing titers against a SARS-CoV-2 D614G pseudovirus increased by a factor of 4 to 73, and binding titers increased by a factor of 5 to 55. Homologous boosters increased neutralizing antibody titers by a factor of 4 to 20, whereas heterologous boosters increased titers by a factor of 6 to 73. Spike-specific T-cell responses increased in all but the homologous Ad26.COV2.S-boosted subgroup. CD8+ T-cell levels were more durable in the Ad26.COV2.S-primed recipients, and heterologous boosting with the Ad26.COV2.S vaccine substantially increased spike-specific CD8+ T cells in the mRNA vaccine recipients.ConclusionsHomologous and heterologous booster vaccines had an acceptable safety profile and were immunogenic in adults who had completed a primary Covid-19 vaccine regimen at least 12 weeks earlier. (Funded by the National Institute of Allergy and Infectious Diseases; DMID 21-0012 ClinicalTrials.gov number, NCT04889209.).Copyright © 2022 Massachusetts Medical Society.

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