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Yan, Jingyi; Bangalore, Chandrashekar Ravenna; Nikouyan, Negin; Appelberg, Sofia; Silva, Daniela Nacimento; Yao, Haidong; Pasetto, Anna; Weber, Friedemann; Weber, Sofie; Larsson, Olivia; Höglund, Urban; Bogdanovic, Gordana; Grabbe, Malin; Aleman, Soo; Szekely, Laszlo; Szakos, Attila; Tuvesson, Ola; Gidlund, Eva-Karin; Cadossi, Matteo; Salati, Simona; Tegel, Hanna; Hober, Sophia; Frelin, Lars; Mirazimi, Ali; Ahlén, Gustaf; Sällberg, Matti
Molecular therapy, 02/2024, Letnik: 32, Številka: 2Journal Article
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. Display omitted Yan and colleagues explores the role of T cells to SARS-CoV-2 in three different challenge models. The study reveals that T cells alone have the ability to limit viral replication, but this may come at a cost of an increase tissue damage by cell killing.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Vir: Osebne bibliografije
in: SICRIS
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