tetano
Editor, Senior Moderator
Nat Immunol
. 2024 Mar 14.
doi: 10.1038/s41590-024-01787-z. Online ahead of print. Antibody-independent protection against heterologous SARS-CoV-2 challenge conferred by prior infection or vaccination
Valeria Fumagalli[SUP] 1 2 [/SUP], Micol Ravà[SUP] 1 2 [/SUP], Davide Marotta[SUP] 1 2 [/SUP], Pietro Di Lucia[SUP] 1 2 [/SUP], Elisa B Bono[SUP] 1 [/SUP], Leonardo Giustini[SUP] 1 [/SUP], Federica De Leo[SUP] 3 [/SUP], Maura Casalgrandi[SUP] 4 [/SUP], Emanuele Monteleone[SUP] 2 [/SUP], Violette Mouro[SUP] 1 [/SUP], Chiara Malpighi[SUP] 1 [/SUP], Chiara Perucchini[SUP] 1 [/SUP], Marta Grillo[SUP] 1 2 [/SUP], Sara De Palma[SUP] 1 5 [/SUP], Lorena Donnici[SUP] 6 [/SUP], Silvia Marchese[SUP] 7 [/SUP], Matteo Conti[SUP] 6 [/SUP], Hiromi Muramatsu[SUP] 8 [/SUP], Stanley Perlman[SUP] 9 10 [/SUP], Norbert Pardi[SUP] 8 [/SUP], Mirela Kuka[SUP] 1 2 [/SUP], Raffaele De Francesco[SUP] #[/SUP][SUP] 6 7 [/SUP], Marco E Bianchi[SUP] #[/SUP][SUP] 11 12 [/SUP], Luca G Guidotti[SUP] #[/SUP][SUP] 13 14 [/SUP], Matteo Iannacone[SUP] #[/SUP][SUP] 15 16 17 [/SUP]
Affiliations
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[SUP]+[/SUP] T cells are essential for combating severe infections, whereas CD4[SUP]+[/SUP] 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.
. 2024 Mar 14.
doi: 10.1038/s41590-024-01787-z. Online ahead of print. Antibody-independent protection against heterologous SARS-CoV-2 challenge conferred by prior infection or vaccination
Valeria Fumagalli[SUP] 1 2 [/SUP], Micol Ravà[SUP] 1 2 [/SUP], Davide Marotta[SUP] 1 2 [/SUP], Pietro Di Lucia[SUP] 1 2 [/SUP], Elisa B Bono[SUP] 1 [/SUP], Leonardo Giustini[SUP] 1 [/SUP], Federica De Leo[SUP] 3 [/SUP], Maura Casalgrandi[SUP] 4 [/SUP], Emanuele Monteleone[SUP] 2 [/SUP], Violette Mouro[SUP] 1 [/SUP], Chiara Malpighi[SUP] 1 [/SUP], Chiara Perucchini[SUP] 1 [/SUP], Marta Grillo[SUP] 1 2 [/SUP], Sara De Palma[SUP] 1 5 [/SUP], Lorena Donnici[SUP] 6 [/SUP], Silvia Marchese[SUP] 7 [/SUP], Matteo Conti[SUP] 6 [/SUP], Hiromi Muramatsu[SUP] 8 [/SUP], Stanley Perlman[SUP] 9 10 [/SUP], Norbert Pardi[SUP] 8 [/SUP], Mirela Kuka[SUP] 1 2 [/SUP], Raffaele De Francesco[SUP] #[/SUP][SUP] 6 7 [/SUP], Marco E Bianchi[SUP] #[/SUP][SUP] 11 12 [/SUP], Luca G Guidotti[SUP] #[/SUP][SUP] 13 14 [/SUP], Matteo Iannacone[SUP] #[/SUP][SUP] 15 16 17 [/SUP]
Affiliations
- PMID: 38486021
- DOI: 10.1038/s41590-024-01787-z
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[SUP]+[/SUP] T cells are essential for combating severe infections, whereas CD4[SUP]+[/SUP] 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.