[저자] Kizzmekia S Corbett, Darin Edwards, Sarah R Leist, Olubukola M Abiona, Seyhan Boyoglu-Barnum, Rebecca A Gillespie, Sunny Himansu, Alexandra Schäfer, Cynthia T Ziwawo, Anthony T DiPiazza, Kenneth H Dinnon, Sayda M Elbashir, Christine A Shaw, Angela Woods, Ethan J Fritch, David R Martinez, Kevin W Bock, Mahnaz Minai, Bianca M Nagata, Geoffrey B Hutchinson, Kapil Bahl, Dario Garcia-Dominguez, LingZhi Ma, Isabella Renzi, Wing-Pui Kong, Stephen D Schmidt, Lingshu Wang, Yi Zhang, Laura J Stevens, Emily Phung, Lauren A Chang, Rebecca J Loomis, Nedim Emil Altaras, Elisabeth Narayanan, Mihir Metkar, Vlad Presnyak, Catherine Liu, Mark K Louder, Wei Shi, Kwanyee Leung, Eun Sung Yang, Ande West, Kendra L Gully, Nianshuang Wang, Daniel Wrapp, Nicole A Doria-Rose, Guillaume Stewart-Jones, Hamilton Bennett, Martha C Nason, Tracy J Ruckwardt, Jason S McLellan, Mark R Denison, James D Chappell, Ian N Moore, Kaitlyn M Morabito, John R Mascola, Ralph S Baric, Andrea Carfi, Barney S Graham
[Category] 비임상,
[Article Type] Article
[Source] PMC
Abstract
A SARS-CoV-2 vaccine is needed to control the global COVID-19 public health crisis. Atomic-level structures directed the application of prefusion-stabilizing mutations that improved expression and immunogenicity of betacoronavirus spike proteins. 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 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 a Phase 2 clinical trial with a trajectory towards Phase 3 efficacy evaluation.
All Keywords
【저자키워드】 breath, 【초록키워드】 COVID-19, neutralizing antibody, Structure, Efficacy, immunogenicity, clinical trial, Mutation, mRNA vaccine, Phase 2, mRNA-1273, SARS-COV-2 infection, lung, immunopathology, public health crisis, Betacoronavirus, SARS-CoV-2 vaccine, Health crisis, T cell, mice, mRNA, response, Lungs, trajectory, expression, Evidence, Spike proteins, CD8 T cell, phase, evidence of, SARS-CoV-2 sequences, SARS-CoV-2 sequence, prefusion, CD8 T cell responses, SARS-CoV-2 spike trimer, PROTECT, induce, triggered, expressing, 【제목키워드】 SARS-CoV-2, development, prototype,
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SARS-CoV-2 백신은 세계적인 COVID-19 공중 보건 위기를 통제하기 위해 필요합니다. 원자 수준 구조는 베타코로나바이러스 스파이크 단백질의 발현과 면역원성을 개선하는 융합전 안정화 돌연변이의 적용을 지시했습니다. 이 확립된 면역원 설계를 사용하여 SARS-CoV-2 서열의 방출은 사전 융합 안정화 SARS-CoV-2 스파이크 삼량체(mRNA-1273)를 발현하는 mRNA 백신의 즉각적인 신속한 제조를 촉발했습니다. 여기에서 우리는 mRNA-1273이 강력한 중화 항체와 CD8 T 세포 반응을 모두 유도하고 면역 병리학의 증거 없이 마우스의 폐와 코에서 SARS-CoV-2 감염을 보호한다는 것을 보여줍니다. mRNA-1273은 현재 3상 효능 평가를 향한 궤적과 함께 2상 임상 시험에 있습니다.