Journalartikel

Autorenliste: 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

Jahr der Veröffentlichung: 2024

Seiten: 540-555

Zeitschrift: Molecular Therapy

Bandnummer: 32

Heftnummer: 2

ISSN: 1525-0016

eISSN: 1525-0024

Open Access Status: Hybrid

DOI Link: https://doi.org/10.1016/j.ymthe.2024.01.007

Verlag: Cell Press

Abstract: 

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2)-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.

Harvard-Zitierstil: Yan, J., Bangalore, C., Nikouyan, N., Appelberg, S., Silva, D., Yao, H., et al. (2024) Distinct roles of vaccine-induced SARS-CoV-2-specific neutralizing antibodies and T cells in protection and disease, Molecular Therapy, 32(2), pp. 540-555. https://doi.org/10.1016/j.ymthe.2024.01.007

APA-Zitierstil: Yan, J., Bangalore, C., Nikouyan, N., Appelberg, S., Silva, D., 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., ...Sällberg, M. (2024). Distinct roles of vaccine-induced SARS-CoV-2-specific neutralizing antibodies and T cells in protection and disease. Molecular Therapy. 32(2), 540-555. https://doi.org/10.1016/j.ymthe.2024.01.007