Ad26.COV2.S priming provides a solid immunological base for mRNA-based COVID-19 booster vaccination
Abstract
Abstract A large proportion of the global population received a single dose of the Ad26.COV2.S coronavirus disease-2019 (COVID-19) vaccine as priming vaccination, which was shown to provide protection against moderate to severe COVID-19. However, the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants that harbor immune-evasive mutations in the spike protein led to the recommendation of booster vaccinations after Ad26.COV2.S priming. Recent studies showed that heterologous booster vaccination with an mRNA-based vaccine following Ad26.COV2.S priming leads to high antibody levels. However, how heterologous booster vaccination affects other functional aspects of the immune response remains unknown. Here, we performed immunological profiling on samples obtained from Ad26.COV2.S-vaccinated individuals before and after a homologous (Ad26.COV2.S) or heterologous (mRNA-1273 or BNT162b2) booster vaccination. Both homologous and heterologous booster vaccination increased antibodies with multiple functionalities towards ancestral SARS-CoV-2, the Delta and Omicron BA.1 variants. Especially, mRNA-based booster vaccination induced high levels of neutralizing antibodies and antibodies with various Fc-mediated effector functions such as antibody-dependent cellular cytotoxicity and phagocytosis. In contrast, T cell responses were similar in magnitude following homologous or heterologous booster vaccination, and retained functionality towards Delta and Omicron BA.1. However, only heterologous booster vaccination with an mRNA-based vaccine led to the expansion of SARS-CoV-2-specific T cell clones, without an increase in the breadth of the T cell repertoire as assessed by T cell receptor sequencing. In conclusion, we show that Ad26.COV2.S priming vaccination provides a solid immunological base for heterologous boosting with an mRNA-based COVID-19 vaccine, increasing humoral and cellular responses targeting newly emerging variants of concern. One sentence summary Ad26.COV2.S priming provides a solid immunological base for extension of cellular and humoral immune responses following an mRNA-based booster.
Authors 24
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Affiliation as printed
Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands
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Affiliation as printed
Department of Hospital Pharmacy, Erasmus Medical Center, Rotterdam, the Netherlands
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University Medical Center Groningen · University of Groningen · National Institute for Public Health and the Environment
Affiliation as printed
Center for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands
Department of Medical Microbiology and Infection Prevention, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
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Amsterdam University Medical Centers · University of Amsterdam
Affiliation as printed
Department of Experimental Immunology, Amsterdam University Medical Centers, Amsterdam Infection and Immunity Institute, University of Amsterdam, Amsterdam, the Netherlands
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Affiliation as printed
Department of Hospital Pharmacy, Erasmus Medical Center, Rotterdam, the Netherlands
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Affiliation as printed
Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands
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Affiliation as printed
Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands
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Affiliation as printed
Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands
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Affiliation as printed
Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands
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Affiliation as printed
Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands
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Affiliation as printed
Department of Hospital Pharmacy, Erasmus Medical Center, Rotterdam, the Netherlands
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Affiliation as printed
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands
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Affiliation as printed
Department of Internal Medicine, Division of Allergy & Clinical Immunology and Department of Immunology, Erasmus Medical Center, Rotterdam, the Netherlands
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Amsterdam Public Health · Amsterdam University Medical Centers · University of Amsterdam
Affiliation as printed
Center of Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Amsterdam University Medical Centers, Amsterdam, the Netherlands
Infection & Immunity, Amsterdam Public Health, University of Amsterdam, Amsterdam, the Netherlands
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University Medical Center Groningen
Affiliation as printed
Department of Internal Medicine and Infectious Diseases, University Medical Center Groningen, Groningen, the Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands
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University Medical Center Groningen · University of Groningen
Affiliation as printed
Department of Medical Microbiology and Infection Prevention, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
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La Jolla Institute for Immunology · University of California San Diego
Affiliation as printed
Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA, USA
Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, CA, USA
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La Jolla Institute for Immunology
Affiliation as printed
Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA, USA
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Affiliation as printed
Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands
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Affiliation as printed
Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands
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Affiliation as printed
Department of Hospital Pharmacy, Erasmus Medical Center, Rotterdam, the Netherlands
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Affiliation as printed
Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands
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Rory D. de Vries corresponding
Affiliation as printed
Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands
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