We generated an optimized COVID-19 vaccine candidate based on the modified vaccinia virus Ankara (MVA) vector expressing a full-length prefusion-stabilized SARS-CoV-2 spike (S) protein, termed MVA-CoV2-S(3P). The S(3P) protein was expressed at higher levels (2-fold) than the non-stabilized S in cells infected with the corresponding recombinant MVA viruses. One single dose of MVA-CoV2-S(3P) induced higher IgG and neutralizing antibody titers against parental SARS-CoV-2 and variants of concern than MVA-CoV2-S in wild-type C57BL/6 and in transgenic K18-hACE2 mice. In immunized C57BL/6 mice, two doses of MVA-CoV2-S or MVA-CoV2-S(3P) induced similar levels of SARS-CoV-2-specific B- and T-cell immune responses. Remarkably, a single administration of MVA-CoV2-S(3P) protected all K18-hACE2 mice from morbidity and mortality caused by SARS-CoV-2 infection, reducing SARS-CoV-2 viral loads, histopathological lesions, and levels of pro-inflammatory cytokines in the lungs. These results demonstrated that expression of a novel full-length prefusion-stabilized SARS-CoV-2 S protein by the MVA poxvirus vector enhanced immunogenicity and efficacy against SARS-CoV-2 in animal models, further supporting MVA-CoV2-S(3P) as an optimized vaccine candidate for clinical trials.
【저자키워드】 SARS-CoV-2 vaccine, mouse model, MVA vector, prefusion-stabilized S protein, protective efficacy, 【초록키워드】 viruses, SARS-CoV-2, IgG, Efficacy, COVID-19 vaccine, immunogenicity, Cytokines, S protein, SARS-COV-2 infection, variants of concern, clinical trials, animal models, variants, hACE2, Protein, Viral, mice, immune responses, Lungs, morbidity, vaccine candidate, K18-hACE2 mice, pro-inflammatory cytokines, morbidity and mortality, poxvirus, expression, Antibody titers, single dose, Neutralizing antibody titer, SARS-CoV-2 spike, SARS-CoV-2 S protein, administration, dose, neutralizing antibody titers, lesions, viral loads, pro-inflammatory cytokine, wild-type, full-length, modified vaccinia virus, SARS-CoV-2 viral loads, C57BL/6, transgenic, Cell, immunized, T-cell immune responses, caused, reducing, expressed, demonstrated, histopathological, expressing, parental, 【제목키워드】 SARS-CoV-2, spike, concern, lethal,