AUTHOR=Metzdorf Kristin , Jacobsen Henning , Kim Yeonsu , Teixeira Alves Luiz Gustavo , Kulkarni Upasana , Brdovčak Maja Cokarić , Materljan Jelena , Eschke Kathrin , Chaudhry M. Zeeshan , Hoffmann Markus , Bertoglio Federico , Ruschig Maximilian , Hust Michael , Šustić Marko , Krmpotić Astrid , Jonjić Stipan , Widera Marek , Ciesek Sandra , Pöhlmann Stefan , Landthaler Markus , Čičin-Šain Luka TITLE=A single-dose MCMV-based vaccine elicits long-lasting immune protection in mice against distinct SARS-CoV-2 variants JOURNAL=Frontiers in Immunology VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1383086 DOI=10.3389/fimmu.2024.1383086 ISSN=1664-3224 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.