Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates

被引：842

作者：

Corbett, Kizzmekia S. ^{[1
]}

Flynn, Barbara ^{[1
]}

Foulds, Kathryn E. ^{[1
]}

Francica, Joseph R. ^{[1
]}

Boyoglu-Barnum, Seyhan ^{[1
]}

Werner, Anne P. ^{[1
]}

Flach, Britta ^{[1
]}

O'Connell, Sarah ^{[1
]}

Bock, Kevin W. ^{[2
]}

Minai, Mahnaz ^{[2
]}

Nagata, Bianca M. ^{[2
]}

Andersen, Hanne ^{[4
]}

Martinez, David R. ^{[6
]}

Noe, Amy T. ^{[1
]}

Douek, Naomi ^{[1
]}

Donaldson, Mitzi M. ^{[1
]}

Nji, Nadesh N. ^{[1
]}

Alvarado, Gabriela S. ^{[1
]}

Edwards, Darin K. ^{[7
]}

Flebbe, Dillon R. ^{[1
]}

Lamb, Evan ^{[1
]}

Doria-Rose, Nicole A. ^{[1
]}

Lin, Bob C. ^{[1
]}

Louder, Mark K. ^{[1
]}

O'Dell, Sijy ^{[1
]}

Schmidt, Stephen D. ^{[1
]}

Phung, Emily ^{[1
,8
]}

Chang, Lauren A. ^{[1
]}

Yap, Christina ^{[1
]}

Todd, John-Paul M. ^{[1
]}

Pessaint, Laurent ^{[4
]}

Van Ry, Alex ^{[4
]}

Browne, Shanai ^{[4
]}

Greenhouse, Jack ^{[4
]}

Putman-Taylor, Tammy ^{[4
]}

Strasbaugh, Amanda ^{[4
]}

Campbell, Tracey-Ann ^{[4
]}

Cook, Anthony ^{[4
]}

Dodson, Alan ^{[4
]}

Steingrebe, Katelyn ^{[4
]}

Shi, Wei ^{[1
]}

Zhang, Yi ^{[1
]}

Abiona, Olubukola M. ^{[1
]}

Wang, Lingshu ^{[1
]}

Pegu, Amarendra ^{[1
]}

Yang, Eun Sung ^{[1
]}

Leung, Kwanyee ^{[1
]}

Zhou, Tongqing ^{[1
]}

Teng, I-Ting ^{[1
]}

Widge, Alicia ^{[1
]}

机构：

[1] NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr, Bethesda, MD 20892 USA

[2] NIAID, Infect Dis Pathogenesis Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[3] NIAID, Biostat Res Branch, Div Clin Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[4] Bioqual, Rockville, MD USA

[5] Public Hlth Serv Commissioned Corps, Rockville, MD USA

[6] Univ North Carolina, Dept Epidemiol, Chapel Hill, NC 27515 USA

[7] Moderna, Cambridge, MA USA

[8] George Washington Univ, Inst Biomed Sci, Washington, DC USA

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2020年 / 383卷 / 16期

基金：

美国国家卫生研究院;

关键词：

LENGTH INFECTIOUS CDNA; REVERSE GENETICS; SPIKE; MERS; IMMUNOGENICITY;

D O I：

10.1056/NEJMoa2024671

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

BackgroundVaccines to prevent coronavirus disease 2019 (Covid-19) are urgently needed. The effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines on viral replication in both upper and lower airways is important to evaluate in nonhuman primates. MethodsNonhuman primates received 10 or 100 mu g of mRNA-1273, a vaccine encoding the prefusion-stabilized spike protein of SARS-CoV-2, or no vaccine. Antibody and T-cell responses were assessed before upper- and lower-airway challenge with SARS-CoV-2. Active viral replication and viral genomes in bronchoalveolar-lavage (BAL) fluid and nasal swab specimens were assessed by polymerase chain reaction, and histopathological analysis and viral quantification were performed on lung-tissue specimens. ResultsThe mRNA-1273 vaccine candidate induced antibody levels exceeding those in human convalescent-phase serum, with live-virus reciprocal 50% inhibitory dilution (ID50) geometric mean titers of 501 in the 10-mu g dose group and 3481 in the 100-mu g dose group. Vaccination induced type 1 helper T-cell (Th1)-biased CD4 T-cell responses and low or undetectable Th2 or CD8 T-cell responses. Viral replication was not detectable in BAL fluid by day 2 after challenge in seven of eight animals in both vaccinated groups. No viral replication was detectable in the nose of any of the eight animals in the 100-mu g dose group by day 2 after challenge, and limited inflammation or detectable viral genome or antigen was noted in lungs of animals in either vaccine group. ConclusionsVaccination of nonhuman primates with mRNA-1273 induced robust SARS-CoV-2 neutralizing activity, rapid protection in the upper and lower airways, and no pathologic changes in the lung. (Funded by the National Institutes of Health and others.) Two injections of an mRNA-based vaccine encoding the SARS-CoV-2 spike protein elicited high levels of neutralizing antibody and Th1 CD4 T-cell responses in rhesus macaques. Two days after challenge of vaccinated animals with intranasal and intratracheal virus, viral replication was undetectable in bronchoalveolar-lavage fluid and nasal secretions.

引用

页码：1544 / 1555

页数：12

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