A single-dose MCMV-based vaccine elicits long-lasting immune protection in mice against distinct SARS-CoV-2 variants

被引:0
|
作者
Metzdorf, Kristin [1 ,2 ,3 ]
Jacobsen, Henning [1 ,2 ,3 ]
Kim, Yeonsu [1 ,2 ,3 ]
Alves, Luiz Gustavo Teixeira [4 ]
Kulkarni, Upasana [1 ,2 ,3 ]
Brdovcak, Maja Cokaric [5 ]
Materljan, Jelena [5 ,6 ]
Eschke, Kathrin [1 ]
Chaudhry, M. Zeeshan [1 ]
Hoffmann, Markus [7 ,8 ]
Bertoglio, Federico [9 ]
Ruschig, Maximilian [9 ]
Hust, Michael [9 ]
Sustic, Marko [5 ]
Krmpotic, Astrid [6 ]
Jonjic, Stipan [5 ]
Widera, Marek [10 ]
Ciesek, Sandra [10 ,11 ,12 ]
Poehlmann, Stefan [7 ,8 ]
Landthaler, Markus [4 ,13 ]
Cicin-Sain, Luka [1 ,2 ,3 ]
机构
[1] Helmholtz Ctr Infect Res, Dept Viral Immunol, Braunschweig, Germany
[2] Joint Venture Helmholtz Ctr Infect Med, Ctr Individualized Infect Med, Hannover, Germany
[3] Hannover Med Sch, Hannover, Germany
[4] Berlin Inst Med Syst Biol BIMSB, Max Delbruck Ctr Mol Med Helmholtz Assoc MDC, Berlin, Germany
[5] Univ Rijeka, Fac Med, Ctr Prote, Rijeka, Croatia
[6] Univ Rijeka, Fac Med, Dept Histol & Embryol, Rijeka, Croatia
[7] Leibniz Inst Primate Res, German Primate Ctr, Infect Biol Unit, Gottingen, Germany
[8] Georg August Univ Gottingen, Fac Biol & Psychol, Gottingen, Germany
[9] Tech Univ Carolo Wilhelmina Braunschweig, Inst Biochem Biotechnol & Bioinformat, Dept Med Biotechnol, Braunschweig, Germany
[10] Goethe Univ Frankfurt, Univ Hosp Frankfurt, Inst Med Virol, Frankfurt, Germany
[11] Fraunhofer Inst Translat Med & Pharmacol ITMP, Frankfurt, Germany
[12] German Ctr Infect Res DZIF, External Partner Site Frankfurt, Frankfurt, Germany
[13] Humboldt Univ, Inst Biol, Berlin, Germany
来源
FRONTIERS IN IMMUNOLOGY | 2024年 / 15卷
关键词
SARS-CoV-2; COVID-19; MCMV; vaccination; single-dose; long-lasting protection; mouse; in vivo; T-CELL RESPONSES; EFFECTOR; ANTIBODIES; INFECTION; INFLATION; BNT162B2;
D O I
10.3389/fimmu.2024.1383086
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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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页数:18
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