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Antibody-independent protection against heterologous SARS-CoV-2 challenge conferred by prior infection or vaccination
Journal article   Open access   Peer reviewed

Antibody-independent protection against heterologous SARS-CoV-2 challenge conferred by prior infection or vaccination

Valeria Fumagalli, Micol Ravà, Davide Marotta, Pietro Di Lucia, Elisa B Bono, Leonardo Giustini, Federica De Leo, Maura Casalgrandi, Emanuele Monteleone, Violette Mouro, …
Nature immunology, Vol.25(4), pp.633-643
04/2024
DOI: 10.1038/s41590-024-01787-z
PMCID: PMC11003867
PMID: 38486021
url
https://doi.org/10.1038/s41590-024-01787-zView
Published (Version of record) Open Access

Abstract

Vaccines have reduced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) morbidity and mortality, yet emerging variants challenge their effectiveness. The prevailing approach to updating vaccines targets the antibody response, operating under the presumption that it is the primary defense mechanism following vaccination or infection. This perspective, however, can overlook the role of T cells, particularly when antibody levels are low or absent. Here we show, through studies in mouse models lacking antibodies but maintaining functional B cells and lymphoid organs, that immunity conferred by prior infection or mRNA vaccination can protect against SARS-CoV-2 challenge independently of antibodies. Our findings, using three distinct models inclusive of a novel human/mouse ACE2 hybrid, highlight that CD8 T cells are essential for combating severe infections, whereas CD4 T cells contribute to managing milder cases, with interferon-γ having an important function in this antibody-independent defense. These findings highlight the importance of T cell responses in vaccine development, urging a broader perspective on protective immunity beyond just antibodies.

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