Journal
FRONTIERS IN IMMUNOLOGY
Volume 12, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.824728
Keywords
SARS-CoV-2 vaccine; MVA vector; prefusion-stabilized S protein; protective efficacy; mouse model
Categories
Funding
- Spanish Health Ministry, Instituto de Salud Carlos III (ISCIII)
- Fondo COVID-19 grant [COV20/00151]
- Fondo Supera COVID-19 (Crue Universidades-Banco Santander) grant
- Spanish Research Council (CSIC) [202120E079]
- CSIC [2020E84, 202020E079]
- La CaixaImpulse grant [CF01-00008]
- Ferrovial donation
- MAPFRE donation
- Spanish Ministry of Science and Innovation (MICINN), Spanish Research Agency [PID2020-114481RB-I00]
- European Commission-NextGenerationEU, through CSIC's Global Health Platform (PTI Salud Global)
- European Commission [731868, EPIC-CROWN-2-2021:101046084]
- Fundacion Caixa-Health Research [HR18-00469]
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Researchers developed an optimized COVID-19 vaccine candidate using a modified vaccinia virus Ankara vector, which expressed a full-length prefusion-stabilized SARS-CoV-2 spike protein. The vaccine showed enhanced immunogenicity and efficacy against SARS-CoV-2 in animal models, making it a promising candidate for clinical trials.
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.
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