Homologous and Heterologous Covid-19 Booster Vaccinations

Robert L Atmar1, Kirsten E Lyke1, Meagan E Deming1

  • 1From 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.

Insights

Homologous and heterologous COVID-19 vaccine boosters are safe and effective. Both increased antibody and T-cell responses, with heterologous boosters showing a greater increase in neutralizing antibody titers.

Area of Science:

  • Immunology
  • Vaccinology
  • Infectious Diseases

Background:

  • Breakthrough infections occur despite high COVID-19 vaccine effectiveness.
  • Data on sequential homologous and heterologous boosters are needed.

Purpose of the Study:

  • To evaluate the safety and immunogenicity of homologous and heterologous COVID-19 vaccine boosters.
  • To compare immune responses following different booster strategies.

Main Methods:

  • Phase 1-2 open-label trial with 458 adults.
  • Participants received homologous or heterologous boosters (mRNA-1273, Ad26.COV2.S, or BNT162b2).
  • Assessed safety, reactogenicity, and humoral immunogenicity.

Main Results:

  • Boosters were generally safe with mild, transient reactogenicity.
  • Both homologous and heterologous boosters significantly increased antibody neutralizing and binding titers.
  • Heterologous boosters showed a greater increase in neutralizing antibody titers compared to homologous boosters.
  • Spike-specific T-cell responses increased, with more durable CD8+ T-cell levels in Ad26.COV2.S-primed recipients.

Conclusions:

  • Homologous and heterologous COVID-19 boosters are safe and immunogenic.
  • Heterologous boosting strategies can enhance immune responses.
Abstract

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