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A single-dose MCMV-based vaccine elicits long-lasting immune protection in mice against distinct SARS-CoV-2 variants

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Item Type:Article
Title:A single-dose MCMV-based vaccine elicits long-lasting immune protection in mice against distinct SARS-CoV-2 variants
Creators Name:Metzdorf, K., Jacobsen, H., Kim, Y., Teixeira Alves, L.G., Kulkarni, U., Brdovčak, M.C., Materljan, J., Eschke, K., Chaudhry, M.Z., Hoffmann, M., Bertoglio, F., Ruschig, M., Hust, M., Šustić, M., Krmpotić, A., Jonjić, S., Widera, M., Ciesek, S., Pöhlmann, S., Landthaler, M. and Čičin-Šain, L.
Abstract:Current vaccines against COVID-19 elicit immune responses that are overall strong but wane rapidly. As a consequence, the necessary booster shots have contributed to vaccine fatigue. Hence, vaccines that would provide lasting protection against COVID-19 are needed, but are still unavailable. Cytomegaloviruses (CMVs) elicit lasting and uniquely strong immune responses. Used as vaccine vectors, they may be attractive tools that obviate the need for boosters. Therefore, we tested the murine CMV (MCMV) as a vaccine vector against COVID-19 in relevant preclinical models of immunization and challenge. We have previously developed a recombinant MCMV vaccine vector expressing the spike protein of the ancestral SARS-CoV-2 (MSMV(S)). In this study, we show that the MSMV(S) elicits a robust and lasting protection in young and aged mice. Notably, spike-specific humoral and cellular immunity was not only maintained but also even increased over a period of at least 6 months. During that time, antibody avidity continuously increased and expanded in breadth, resulting in neutralization of genetically distant variants, like Omicron BA.1. A single dose of MSMV(S) conferred rapid virus clearance upon challenge. Moreover, MSMV(S) vaccination controlled two variants of concern (VOCs), the Beta (B.1.135) and the Omicron (BA.1) variants. Thus, CMV vectors provide unique advantages over other vaccine technologies, eliciting broadly reactive and long-lasting immune responses against COVID-19.
Keywords:SARS-CoV-2, COVID-19, MCMV, Vaccination, Single-Dose, Long-Lasting Protection, Mouse, In Vivo, Animals, Mice
Source:Frontiers in Immunology
ISSN:1664-3224
Publisher:Frontiers Media SA
Volume:15
Page Range:1383086
Date:25 July 2024
Official Publication:https://doi.org/10.3389/fimmu.2024.1383086
PubMed:View item in PubMed

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