Frontiers in Immunology (Jul 2024)
A single-dose MCMV-based vaccine elicits long-lasting immune protection in mice against distinct SARS-CoV-2 variants
- Kristin Metzdorf,
- Kristin Metzdorf,
- Henning Jacobsen,
- Henning Jacobsen,
- Yeonsu Kim,
- Yeonsu Kim,
- Luiz Gustavo Teixeira Alves,
- Upasana Kulkarni,
- Upasana Kulkarni,
- Maja Cokarić Brdovčak,
- Jelena Materljan,
- Jelena Materljan,
- Kathrin Eschke,
- M. Zeeshan Chaudhry,
- Markus Hoffmann,
- Markus Hoffmann,
- Federico Bertoglio,
- Maximilian Ruschig,
- Michael Hust,
- Marko Šustić,
- Astrid Krmpotić,
- Stipan Jonjić,
- Marek Widera,
- Sandra Ciesek,
- Sandra Ciesek,
- Sandra Ciesek,
- Stefan Pöhlmann,
- Stefan Pöhlmann,
- Markus Landthaler,
- Markus Landthaler,
- Luka Čičin-Šain,
- Luka Čičin-Šain
Affiliations
- Kristin Metzdorf
- Department of Viral Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany
- Kristin Metzdorf
- Centre for Individualized Infection Medicine, a Joint Venture of the Helmholtz Centre for Infection Medicine and the Hannover Medical School, Hannover, Germany
- Henning Jacobsen
- Department of Viral Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany
- Henning Jacobsen
- Centre for Individualized Infection Medicine, a Joint Venture of the Helmholtz Centre for Infection Medicine and the Hannover Medical School, Hannover, Germany
- Yeonsu Kim
- Department of Viral Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany
- Yeonsu Kim
- Centre for Individualized Infection Medicine, a Joint Venture of the Helmholtz Centre for Infection Medicine and the Hannover Medical School, Hannover, Germany
- Luiz Gustavo Teixeira Alves
- Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
- Upasana Kulkarni
- Department of Viral Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany
- Upasana Kulkarni
- Centre for Individualized Infection Medicine, a Joint Venture of the Helmholtz Centre for Infection Medicine and the Hannover Medical School, Hannover, Germany
- Maja Cokarić Brdovčak
- Center for Proteomics, University of Rijeka, Faculty of Medicine, Rijeka, Croatia
- Jelena Materljan
- Center for Proteomics, University of Rijeka, Faculty of Medicine, Rijeka, Croatia
- Jelena Materljan
- Department of Histology and Embryology, University of Rijeka, Faculty of Medicine, Rijeka, Croatia
- Kathrin Eschke
- Department of Viral Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany
- M. Zeeshan Chaudhry
- Department of Viral Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany
- Markus Hoffmann
- Infection Biology Unit, German Primate Center – Leibniz Institute for Primate Research, Göttingen, Germany
- Markus Hoffmann
- Faculty of Biology and Psychology, Georg-August-University Göttingen, Göttingen, Germany
- Federico Bertoglio
- Department of Medical Biotechnology, Institute for Biochemistry, Biotechnology and Bioinformatics, Technische Universität Braunschweig, Braunschweig, Germany
- Maximilian Ruschig
- Department of Medical Biotechnology, Institute for Biochemistry, Biotechnology and Bioinformatics, Technische Universität Braunschweig, Braunschweig, Germany
- Michael Hust
- Department of Medical Biotechnology, Institute for Biochemistry, Biotechnology and Bioinformatics, Technische Universität Braunschweig, Braunschweig, Germany
- Marko Šustić
- Center for Proteomics, University of Rijeka, Faculty of Medicine, Rijeka, Croatia
- Astrid Krmpotić
- Department of Histology and Embryology, University of Rijeka, Faculty of Medicine, Rijeka, Croatia
- Stipan Jonjić
- Center for Proteomics, University of Rijeka, Faculty of Medicine, Rijeka, Croatia
- Marek Widera
- Institute for Medical Virology, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt am Main, Germany
- Sandra Ciesek
- Institute for Medical Virology, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt am Main, Germany
- Sandra Ciesek
- 0Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt am Main, Germany
- Sandra Ciesek
- 1German Centre for Infection Research (DZIF), External Partner Site Frankfurt, Frankfurt, Germany
- Stefan Pöhlmann
- Infection Biology Unit, German Primate Center – Leibniz Institute for Primate Research, Göttingen, Germany
- Stefan Pöhlmann
- Faculty of Biology and Psychology, Georg-August-University Göttingen, Göttingen, Germany
- Markus Landthaler
- Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
- Markus Landthaler
- 2Institute for Biology, Humboldt-Universität zu Berlin, Berlin, Germany
- Luka Čičin-Šain
- Department of Viral Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany
- Luka Čičin-Šain
- Centre for Individualized Infection Medicine, a Joint Venture of the Helmholtz Centre for Infection Medicine and the Hannover Medical School, Hannover, Germany
- DOI
- https://doi.org/10.3389/fimmu.2024.1383086
- Journal volume & issue
-
Vol. 15
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 (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 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 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.
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