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A combination of vaccination approaches will likely be necessary to fully control the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Here, we show that modified vaccinia Ankara (MVA) vectors expressing membrane-anchored pre-fusion stabilized spike (MVA/S) but not secreted S1 induced strong neutralizing antibody responses against SARS-CoV-2 in mice. In macaques, the MVA/S vaccination induced strong neutralizing antibodies and CD8 T cell responses, and conferred protection from SARS-CoV-2 infection and virus replication in the lungs as early as day 2 following intranasal and intratracheal challenge. Single-cell RNA sequencing analysis of lung cells on day 4 after infection revealed that MVA/S vaccination also protected macaques from infection-induced inflammation and B cell abnormalities and lowered induction of interferon-stimulated genes. These results demonstrate that MVA/S vaccination induces neutralizing antibodies and CD8 T cells in the blood and lungs and is a potential vaccine candidate for SARS-CoV-2.
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http://dx.doi.org/10.1016/j.immuni.2021.02.001 | DOI Listing |
J Med Virol
January 2025
National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing, China.
Oncolytic viruses are emerging as promising cancer therapeutic agents, with several poxviruses, including vaccinia virus (VACV) and myxoma virus, showing significant potential in preclinical and clinical trials. Modified vaccinia virus Ankara (MVA), a laboratory-derived VACV strain approved by the FDA for mpox and smallpox vaccination, has been shown to be incapable of replicating in human cells unless zinc finger antiviral protein (ZAP) is repressed. Notably, ZAP deficiency is prevalent in various cancer types.
View Article and Find Full Text PDFFront Immunol
September 2024
Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
J Virol
July 2024
National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing, China.
Unlabelled: The reoccurrence of successive waves of SARS-CoV-2 variants suggests the exploration of more vaccine alternatives is imperative. Modified vaccinia virus Ankara (MVA) is a virus vector exhibiting excellent safety as well as efficacy for vaccine development. Here, a series of recombinant MVAs (rMVAs) expressing monomerized or trimerized S proteins from different SARS-CoV-2 variants are engineered.
View Article and Find Full Text PDFFront Immunol
January 2024
Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
The constant appearance of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VoCs) has jeopardized the protective capacity of approved vaccines against coronavirus disease-19 (COVID-19). For this reason, the generation of new vaccine candidates adapted to the emerging VoCs is of special importance. Here, we developed an optimized COVID-19 vaccine candidate using the modified vaccinia virus Ankara (MVA) vector to express a full-length prefusion-stabilized SARS-CoV-2 spike (S) protein, containing 3 proline (3P) substitutions in the S protein derived from the beta (B.
View Article and Find Full Text PDFAntiviral Res
December 2023
Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain. Electronic address:
Unravelling the molecular mechanism of COVID-19 vaccines through transcriptomic pathways involved in the host response to SARS-CoV-2 infection is key to understand how vaccines work, and for the development of optimized COVID-19 vaccines that can prevent the emergence of SARS-CoV-2 variants of concern (VoCs) and future outbreaks. In this study, we investigated the effects of vaccination with a modified vaccinia virus Ankara (MVA)-based vector expressing the full-length SARS-CoV-2 spike protein (MVA-S) on the lung transcriptome from susceptible K18-hACE2 mice after SARS-CoV-2 infection. One dose of MVA-S regulated genes related to viral infection control, inflammation processes, T-cell response, cytokine production and IFN-γ signalling.
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