SARS-CoV-2 mRNA Vaccine Design Enabled by Prototype Pathogen Preparedness

A severe acute respiratory syndrome coronavirus (SARS-CoV-2) vaccine is needed to control the global coronavirus infectious disease (COVID-19) public health crisis. Atomic-level structures directed the application of prefusion-stabilizing mutations that improved expression and immunogenicity of beta...

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Detalles Bibliográficos
Autores principales: Corbett, Kizzmekia S., Edwards, Darin K., Leist, Sarah R., Abiona, Olubukola M., Boyoglu-Barnum, Seyhan, Gillespie, Rebecca A., Himansu, Sunny, Schäfer, Alexandra, Ziwawo, Cynthia T., DiPiazza, Anthony T., Dinnon, Kenneth H., Elbashir, Sayda M., Shaw, Christine A., Woods, Angela, Fritch, Ethan J., Martinez, David R., Bock, Kevin W., Minai, Mahnaz, Nagata, Bianca M., Hutchinson, Geoffrey B., Wu, Kai, Henry, Carole, Bahi, Kapil, Garcia-Dominguez, Dario, Ma, LingZhi, Renzi, Isabella, Kong, Wing-Pui, Schmidt, Stephen D., Wang, Lingshu, Zhang, Yi, Phung, Emily, Chang, Lauren A., Loomis, Rebecca J., Altaras, Nedim Emil, Narayanan, Elisabeth, Metkar, Mihir, Presnyak, Vlad, Liu, Cuiping, Louder, Mark K., Shi, Wei, Leung, Kwanyee, Yang, Eun Sung, West, Ande, Gully, Kendra L., Stevens, Laura J., Wang, Nianshuang, Wrapp, Daniel, Doria-Rose, Nicole A., Stewart-Jones, Guillaume, Bennett, Hamilton, Alvarado, Gabriela S., Nason, Martha C., Ruckwardt, Tracy J., McLellan, Jason S., Denison, Mark R., Chappell, James D., Moore, Ian N., Morabito, Kaitlyn M., Mascola, John R., Baric, Ralph S., Carfi, Andrea, Graham, Barney S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2020
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581537/
https://www.ncbi.nlm.nih.gov/pubmed/32756549
http://dx.doi.org/10.1038/s41586-020-2622-0
Descripción
Sumario:A severe acute respiratory syndrome coronavirus (SARS-CoV-2) vaccine is needed to control the global coronavirus infectious disease (COVID-19) public health crisis. Atomic-level structures directed the application of prefusion-stabilizing mutations that improved expression and immunogenicity of betacoronavirus spike proteins(1). Using this established immunogen design, the release of SARS-CoV-2 sequences triggered immediate rapid manufacturing of an mRNA vaccine expressing the prefusion-stabilized SARS-CoV-2 spike trimer (mRNA-1273). Here, we show that mRNA-1273 induces both potent neutralizing antibody responses to wild-type (D614) and D614G mutant(2) SARS-CoV-2 and CD8 T cell responses and protects against SARS-CoV-2 infection in lungs and noses of mice without evidence of immunopathology. mRNA-1273 is currently in Phase 3 efficacy evaluation.

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