Distinct roles of vaccine-induced SARS-CoV-2-specific neutralizing antibodies and T cells in protection and disease.
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Yan J, Bangalore CR, Nikouyan N, Appelberg S, Silva DN, Yao H, Pasetto A, Weber F, Weber S, Larsson O, Höglund U, Bogdanovic G, Grabbe M, Aleman S, Szekely L, Szakos A, Tuvesson O, Gidlund E, Cadossi M, Salati S, Tegel H, Hober S, Frelin L, Mirazimi A, Ahlén G, Sällberg M
Mol Ther 32 (2) 540-555 [2024-02-07; online 2024-01-11]
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific neutralizing antibodies (NAbs) lack cross-reactivity between SARS-CoV species and variants and fail to mediate long-term protection against infection. The maintained protection against severe disease and death by vaccination suggests a role for cross-reactive T cells. We generated vaccines containing sequences from the spike or receptor binding domain, the membrane and/or nucleoprotein that induced only T cells, or T cells and NAbs, to understand their individual roles. In three models with homologous or heterologous challenge, high levels of vaccine-induced SARS-CoV-2 NAbs protected against neither infection nor mild histological disease but conferred rapid viral control limiting the histological damage. With no or low levels of NAbs, vaccine-primed T cells, in mice mainly CD8+ T cells, partially controlled viral replication and promoted NAb recall responses. T cells failed to protect against histological damage, presumably because of viral spread and subsequent T cell-mediated killing. Neither vaccine- nor infection-induced NAbs seem to provide long-lasting protective immunity against SARS-CoV-2. Thus, a more realistic approach for universal SARS-CoV-2 vaccines should be to aim for broadly cross-reactive NAbs in combination with long-lasting highly cross-reactive T cells. Long-lived cross-reactive T cells are likely key to prevent severe disease and fatalities during current and future pandemics.
PubMed 38213030
DOI 10.1016/j.ymthe.2024.01.007
Crossref 10.1016/j.ymthe.2024.01.007
pii: S1525-0016(24)00007-8