tetano
Editor, Senior Moderator
Front Immunol
. 2024 Jul 25:15:1383086.
doi: 10.3389/fimmu.2024.1383086. eCollection 2024. A single-dose MCMV-based vaccine elicits long-lasting immune protection in mice against distinct SARS-CoV-2 variants
Kristin Metzdorf[SUP] #[/SUP][SUP] 1 2 [/SUP], Henning Jacobsen[SUP] #[/SUP][SUP] 1 2 [/SUP], Yeonsu Kim[SUP] #[/SUP][SUP] 1 2 [/SUP], Luiz Gustavo Teixeira Alves[SUP] 3 [/SUP], Upasana Kulkarni[SUP] 1 2 [/SUP], Maja Cokarić Brdovčak[SUP] 4 [/SUP], Jelena Materljan[SUP] 4 5 [/SUP], Kathrin Eschke[SUP] 1 [/SUP], M Zeeshan Chaudhry[SUP] 1 [/SUP], Markus Hoffmann[SUP] 6 7 [/SUP], Federico Bertoglio[SUP] 8 [/SUP], Maximilian Ruschig[SUP] 8 [/SUP], Michael Hust[SUP] 8 [/SUP], Marko Šustić[SUP] 4 [/SUP], Astrid Krmpotić[SUP] 5 [/SUP], Stipan Jonjić[SUP] 4 [/SUP], Marek Widera[SUP] 9 [/SUP], Sandra Ciesek[SUP] 9 10 11 [/SUP], Stefan Pöhlmann[SUP] 6 7 [/SUP], Markus Landthaler[SUP] 3 12 [/SUP], Luka Čičin-Šain[SUP] 1 2 [/SUP]
Affiliations
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 (MCMV[SUP]S[/SUP]). In this study, we show that the MCMV[SUP]S[/SUP] 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 MCMV[SUP]S[/SUP] conferred rapid virus clearance upon challenge. Moreover, MCMV[SUP]S[/SUP] 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.
. 2024 Jul 25:15:1383086.
doi: 10.3389/fimmu.2024.1383086. eCollection 2024. A single-dose MCMV-based vaccine elicits long-lasting immune protection in mice against distinct SARS-CoV-2 variants
Kristin Metzdorf[SUP] #[/SUP][SUP] 1 2 [/SUP], Henning Jacobsen[SUP] #[/SUP][SUP] 1 2 [/SUP], Yeonsu Kim[SUP] #[/SUP][SUP] 1 2 [/SUP], Luiz Gustavo Teixeira Alves[SUP] 3 [/SUP], Upasana Kulkarni[SUP] 1 2 [/SUP], Maja Cokarić Brdovčak[SUP] 4 [/SUP], Jelena Materljan[SUP] 4 5 [/SUP], Kathrin Eschke[SUP] 1 [/SUP], M Zeeshan Chaudhry[SUP] 1 [/SUP], Markus Hoffmann[SUP] 6 7 [/SUP], Federico Bertoglio[SUP] 8 [/SUP], Maximilian Ruschig[SUP] 8 [/SUP], Michael Hust[SUP] 8 [/SUP], Marko Šustić[SUP] 4 [/SUP], Astrid Krmpotić[SUP] 5 [/SUP], Stipan Jonjić[SUP] 4 [/SUP], Marek Widera[SUP] 9 [/SUP], Sandra Ciesek[SUP] 9 10 11 [/SUP], Stefan Pöhlmann[SUP] 6 7 [/SUP], Markus Landthaler[SUP] 3 12 [/SUP], Luka Čičin-Šain[SUP] 1 2 [/SUP]
Affiliations
- PMID: 39119342
- PMCID: PMC11306140
- DOI: 10.3389/fimmu.2024.1383086
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 (MCMV[SUP]S[/SUP]). In this study, we show that the MCMV[SUP]S[/SUP] 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 MCMV[SUP]S[/SUP] conferred rapid virus clearance upon challenge. Moreover, MCMV[SUP]S[/SUP] 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.