Ad26.COV2.S priming provided a solid immunological base for mRNA-based COVID-19 booster vaccination

SWITCH Research Group, Daryl Geers, Roos S.G. Sablerolles, Debbie van Baarle, Neeltje A. Kootstra, Wim J.R. Rietdijk, Katharina S. Schmitz, Lennert Gommers, Susanne Bogers, Nella J. Nieuwkoop, Laura L.A. van Dijk, Eva van Haren, Melvin Lafeber, Virgil A.S.H. Dalm, Abraham Goorhuis, Douwe F. Postma, Leo G. Visser, Anke L.W. Huckriede, Alessandro Sette, Alba GrifoniRik L. de Swart, Marion P.G. Koopmans, P. Hugo M. van der Kuy, Corine H. GeurtsvanKessel, Rory D. de Vries*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Scopus)
35 Downloads (Pure)


The emergence of novel SARS-CoV-2 variants led to the recommendation of booster vaccinations after Ad26.COV2.S priming. It was previously shown that heterologous booster vaccination induces high antibody levels, but how heterologous boosters affect other functional aspects of the immune response remained unknown. Here, we performed immunological profiling of Ad26.COV2.S-primed individuals before and after homologous or heterologous (mRNA-1273 or BNT162b2) booster. Booster vaccinations increased functional antibodies targeting ancestral SARS-CoV-2 and emerging variants. Especially heterologous booster vaccinations induced high levels of functional antibodies. In contrast, T-cell responses were similar in magnitude following homologous or heterologous booster vaccination and retained cross-reactivity towards variants. Booster vaccination led to a minimal expansion of SARS-CoV-2-specific T-cell clones and no increase in the breadth of the T-cell repertoire. In conclusion, we show that Ad26.COV2.S priming vaccination provided a solid immunological base for heterologous boosting, increasing humoral and cellular responses targeting emerging variants of concern.

Original languageEnglish
Article number105753
Number of pages22
Issue number1
Publication statusPublished - 20-Jan-2023


  • Health sciences
  • immune response
  • immunology
  • virology


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