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.
Keywords:
COVID-19; MCMV; SARS-CoV-2; in vivo; long-lasting protection; mouse; single-dose; vaccination.
Copyright © 2024 Metzdorf, Jacobsen, Kim, Teixeira Alves, Kulkarni, Brdovčak, Materljan, Eschke, Chaudhry, Hoffmann, Bertoglio, Ruschig, Hust, Šustić, Krmpotić, Jonjić, Widera, Ciesek, Pöhlmann, Landthaler and Čičin-Šain.
MeSH terms
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Animals
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Antibodies, Neutralizing / blood
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Antibodies, Neutralizing / immunology
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Antibodies, Viral* / blood
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Antibodies, Viral* / immunology
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COVID-19 Vaccines* / immunology
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COVID-19* / immunology
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COVID-19* / prevention & control
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Disease Models, Animal
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Female
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Genetic Vectors
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Humans
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Immunity, Cellular
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Immunity, Humoral
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Mice
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Mice, Inbred BALB C
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Muromegalovirus / genetics
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Muromegalovirus / immunology
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SARS-CoV-2* / genetics
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SARS-CoV-2* / immunology
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Spike Glycoprotein, Coronavirus* / genetics
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Spike Glycoprotein, Coronavirus* / immunology
Substances
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COVID-19 Vaccines
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Spike Glycoprotein, Coronavirus
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Antibodies, Viral
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spike protein, SARS-CoV-2
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Antibodies, Neutralizing
Grants and funding
The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was supported by the grant 14-76103-84 from the Ministry of Science and Culture of Lower Saxony to LČ-Š and by the following grants from the Helmholtz Association’s Impulse and Networking Fund: (i) EU Partnering grant MCMVaccine (PEI-008) to LČ-Š and SJ, and (ii) “Virological and immunological determinants of COVID-19 pathogenesis—lessons to get prepared for future pandemics (KA1-Co-02 “COVIPA”)” to LČ-Š and ML. This work has been supported in part by the grant “Strengthening the capacity of CerVirVac for research in virus immunology and vaccinology”, KK.01.1.1.01.0006, awarded to the Scientific Centre of Excellence for Virus Immunology and Vaccines and co-financed by the European Regional Development Fund and by the Croatian Science Foundation under the project IP-CORONA-04-2055 (AK). We thank the Peter and Traudl Engelhorn foundation for providing a post-doctoral fellowship to HJ. Furthermore, we would like to thank the MDC/BIH@Charite Genomics Technology Platform for sequencing.