A single-dose MCMV-based vaccine elicits long-lasting immune protection in mice against distinct SARS-CoV-2 variants
Abstract 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 MCMVSelicits a robust and lasting protection in young and aged mice. Notably, S-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 MCMVSconferred rapid virus clearance upon challenge. Moreover, MCMVSvaccination controlled two immune-evading 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.Authors Summary While widespread vaccination has substantially reduced risks of severe COVID presentations and morbidity, immune waning and continuous immune escape of novel SARS-CoV-2 variants have resulted in a need for numerous vaccine boosters and a continuous adaptation of vaccines to new SARS-CoV-2 variants. We show in proof of principle experiments with a recombinant murine cytomegalovirus expressing the SARS-CoV-2 spike protein (MCMVS) that one immunization with a CMV vaccine vector drives enduring protection in both young and aged mice, with long-term maturation of immune responses that broaden the antiviral effects over time. Hence, this approach resolves issues of immune waning and mitigates the effects of COVID-19 evolution and immune escape, reducing the need for additional immunizations and potentially improving vaccine compliance..
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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
bioRxiv.org - (2024) vom: 19. Feb. Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Metzdorf, Kristin [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2022.11.25.517953 |
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| PPN (Katalog-ID): |
XBI038011948 |
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| 520 | |a Abstract 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 MCMVSelicits a robust and lasting protection in young and aged mice. Notably, S-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 MCMVSconferred rapid virus clearance upon challenge. Moreover, MCMVSvaccination controlled two immune-evading 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.Authors Summary While widespread vaccination has substantially reduced risks of severe COVID presentations and morbidity, immune waning and continuous immune escape of novel SARS-CoV-2 variants have resulted in a need for numerous vaccine boosters and a continuous adaptation of vaccines to new SARS-CoV-2 variants. We show in proof of principle experiments with a recombinant murine cytomegalovirus expressing the SARS-CoV-2 spike protein (MCMVS) that one immunization with a CMV vaccine vector drives enduring protection in both young and aged mice, with long-term maturation of immune responses that broaden the antiviral effects over time. Hence, this approach resolves issues of immune waning and mitigates the effects of COVID-19 evolution and immune escape, reducing the need for additional immunizations and potentially improving vaccine compliance. | ||
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