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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Viral Immunology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1383086

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

Provisionally accepted
  • 1 Viral Immunology, Helmholtz Center for Infection Research, Helmholtz Association of German Research Centers (HZ), Braunschweig, Niedersachsen, Germany
  • 2 The Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Helmholtz Association of German Research Centers (HZ), Berlin, Baden-Württemberg, Germany
  • 3 Infection Biology Unit, German Primate Center, Leibniz Institute for Primate, Göttingen, Lower Saxony, Germany
  • 4 Faculty of Biology and Psychology, University of Göttingen, Göttingen, Lower Saxony, Germany
  • 5 Institut für Biochemie, Biotechnologie und Bioinformatik, Technische Universitat Braunschweig, Braunschweig, Berlin, Germany
  • 6 Center for Proteomics, Faculty of Medicine, University of Rijeka, Rijeka, Croatia
  • 7 Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia
  • 8 Institute of Medical Virology, Goethe University Frankfurt am Main, Frankfurt, Hesse, Germany
  • 9 Center for Translational Medicine and Pharmacology, Faculty of Medicine, Goethe University Frankfurt am Main, Frankfurt, Hesse, Germany
  • 10 German Center for Infection Research (DZIF), Braunschweig, Germany
  • 11 Institute for Biology, Faculty of Life Sciences, Humboldt University of Berlin, Berlin, Germany
  • 12 Centre for Individualised Infection Medicine, Helmholtz Center for Infection Research, Helmholtz Association of German Research Centers (HZ), Hannover, Germany

The final, formatted version of the article will be published soon.

    Current vaccines against COVID-19 elicit immune responses that are overall strong but wane rapidly. As a consequence, the necessary booster shots have led to vaccine fatigue. Hence, vaccines that would provide lasting protection against COVID-19 are needed, but are still unavailable. Cytomegaloviruses (CMV) 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 murine CMV (MCMV) vaccine vector expressing the spike protein of the ancestral SARS-CoV-2 (MCMVS). In this study, we show that the MCMVS elicits a robust and lasting protection in young and aged mice. Notably, spike-specific humoral and cellular immunity was not only maintained but 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 MCMVS conferred rapid virus clearance upon challenge. Moreover, MCMVS 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

    Received: 06 Feb 2024; Accepted: 11 Jun 2024.

    Copyright: © 2024 Metzdorf, Jacobsen, Kim, Teixeira Alves, Kulkarni, Eschke, Chaudhry, Hoffmann, Bertoglio, Ruschig, Hust, Brdovčak, Materljan, Šustić, Krmpotic, Jonjic, Widera, Ciesek, Pöhlmann, Landthaler and Cicin-Sain. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Luka Cicin-Sain, Viral Immunology, Helmholtz Center for Infection Research, Helmholtz Association of German Research Centers (HZ), Braunschweig, 38124, Niedersachsen, Germany

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.