Immunogenicity and efficacy of the COVID-19 candidate vector vaccine MVA-SARS-2-S in preclinical vaccination

被引:75
作者
Tscherne, Alina [1 ,2 ]
Schwarz, Jan Hendrik [1 ]
Rohde, Cornelius [3 ,4 ]
Kupke, Alexandra [3 ,4 ]
Kalodimou, Georgia [1 ,2 ]
Limpinsel, Leonard [1 ]
Okba, Nisreen M. A. [5 ]
Bosnjak, Berislav [6 ]
Sandrock, Inga [6 ]
Odak, Ivan [6 ]
Halwe, Sandro [3 ,4 ]
Sauerhering, Lucie [3 ,4 ]
Brosinski, Katrin [1 ]
Nan, Liangliang [1 ]
Duell, Elke [1 ,2 ]
Jany, Sylvia [1 ]
Freudenstein, Astrid [1 ]
Schmidt, Joerg [3 ,4 ]
Werner, Anke [3 ,4 ]
Serra, Michelle Gellhorn [3 ,4 ]
Kluever, Michael [3 ,4 ]
Guggemos, Wolfgang [7 ]
Seilmaier, Michael [7 ]
Wendtner, Clemens-Martin [7 ]
Foerster, Reinhold [6 ,8 ,9 ]
Haahmans, Bart L. [5 ]
Becker, Stephan [3 ,4 ]
Sutter, Gerd [1 ,2 ]
Volz, Asisa [1 ,2 ,10 ]
机构
[1] Ludwig Maximilians Univ Munchen, Div Virol, Dept Vet Sci, D-80539 Munich, Germany
[2] German Ctr Infect Res, Dept Vet Sci, Div Virol, D-80539 Munich, Germany
[3] Philipps Univ Marburg, Inst Virol, D-35037 Marburg, Germany
[4] German Ctr Infect Res, Inst Virol, Giessen, Germany
[5] Erasmus MC, Dept Virosci, NL-3015 CN Rotterdam, Netherlands
[6] Hannover Med Sch, Inst Immunol, D-30625 Hannover, Germany
[7] Ludwig Maximilians Univ Munchen, Acad Teaching Hosp, Munich Clin Schwabing, D-80804 Munich, Germany
[8] German Ctr Infect Res, Inst Immunol, D-30625 Hannover, Germany
[9] Hannover Med Sch, Cluster Excellence RESIST, EXC 2155, D-30625 Hannover, Germany
[10] Univ Vet Med, Inst Virol, D-30559 Hannover, Germany
关键词
vaccine vector; vaccinia virus; poxvirus; nonclinical testing; CORONAVIRUS SPIKE PROTEIN; INFECTION;
D O I
10.1073/pnas.2026207118
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) has emerged as the infectious agent causing the pandemic coronavi-rus disease 2019 (COVID-19) with dramatic consequences for global human health and economics. Previously, we reached clinical evalua-tion with our vector vaccine based on modified vaccinia virus Ankara (MVA) against the Middle East respiratory syndrome coronavirus (MERS-CoV), which causes an infection in humans similar to SARS and COVID-19. Here, we describe the construction and preclinical char-acterization of a recombinant MVA expressing full-length SARS-CoV-2 spike (S) protein (MVA-SARS-2-S). Genetic stability and growth char-acteristics of MVA-SARS-2-S, plus its robust expression of S protein as antigen, make it a suitable candidate vaccine for industrial-scale pro-duction. Vaccinated mice produced S-specific CD8(+) T cells and serum antibodies binding to S protein that neutralized SARS-CoV-2. Prime -boost vaccination with MVA-SARS-2-S protected mice sensitized with a human ACE2-expressing adenovirus from SARS-CoV-2 infection. MVA-SARS-2-S is currently being investigated in a phase I clinical trial as aspirant for developing a safe and efficacious vaccine against COVID-19.
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页数:9
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