美国国立卫生研究院Robert A. Seder和Barney S. Graham团队评估了SARS-CoV-2疫苗mRNA-1273在非人灵长类动物中的疗效。2020年7月28日，《新英格兰医学杂志》发表了这一成果。

目前急需预防Covid-19的疫苗。SARS-CoV-2疫苗对非人灵长类动物上、下呼吸道病毒复制的影响具有重要意义。

研究组为非人灵长类动物接种10或100μg的mRNA-1273（一种编码SARS-CoV-2融合前稳定刺突蛋白的疫苗），或不接种疫苗。在使用SARS-CoV-2攻击上、下气道前，评估了抗体和T细胞反应。通过聚合酶链反应评估支气管肺泡灌洗液（BAL）和鼻拭子标本中的活性病毒复制和病毒基因组，并对肺组织标本进行组织病理学分析和病毒定量。

在10μg剂量组和100μg剂量组中，活病毒50%抑制稀释度（ID₅₀）几何平均滴度分别为501和3481。疫苗诱导的1型辅助性T细胞（Th1）偏向CD4 T细胞反应，Th2或CD8 T细胞反应低或不可检测。在两个接种疫苗组中的8只动物中，有7只在攻击后第2天，BAL液中均未检测到病毒复制。在攻击后的第2天，100μg剂量组中8只动物的鼻腔中均未检测到病毒复制，但在两个接种疫苗组的动物肺部发现了有限的炎症或可检测的病毒基因组或抗原。 

总之，用mRNA-1273接种非人灵长类动物可诱导强大的SARS-CoV-2中和活性，在上、下呼吸道中提供快速保护，并且肺部无病理变化。

附：英文原文

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

Author: Kizzmekia S. Corbett, Ph.D.,, Barbara Flynn, M.S.,, Kathryn E. Foulds, Ph.D.,, Joseph R. Francica, Ph.D.,, Seyhan Boyoglu-Barnum, Ph.D.,, Anne P. Werner, B.S.,, Britta Flach, Ph.D.,, Sarah O’Connell, M.S.,, Kevin W. Bock, M.B.,, Mahnaz Minai, M.S.,, Bianca M. Nagata, M.S.,, Hanne Anderson, Ph.D.,, David R. Martinez, Ph.D.,, Amy T. Noe, M.S.,, Naomi Douek,, Mitzi M. Donaldson, M.S.,, Nadesh N. Nji, M.S.,, Gabriela S. Alvarado, Ph.D.,, Darin K. Edwards, Ph.D.,, Dillon R. Flebbe, B.S.,, Evan Lamb, B.S.,, Nicole A. Doria-Rose, Ph.D.,, Bob C. Lin, B.S.,, Mark K. Louder,, Sijy O’Dell, M.S.,, Stephen D. Schmidt, B.S.,, Emily Phung, B.S.,, Lauren A. Chang, B.S.,, Christina Yap, B.S.,, John-Paul M. Todd, B.S.,, Laurent Pessaint, M.S.,, Alex Van Ry, B.S.,, Shanai Browne, B.S.,, Jack Greenhouse, M.S.,, Tammy Putman-Taylor, B.S.,, Amanda Strasbaugh, B.S.,, Tracey-Ann Campbell, B.S.,, Anthony Cook, D.V.M.,, Alan Dodson,, Katelyn Steingrebe,, Wei Shi, Ph.D.,, Yi Zhang, B.S.,, Olubukola M. Abiona, B.S.,, Lingshu Wang, Ph.D.,, Amarendra Pegu, Ph.D.,, Eun Sung Yang, M.S.,, Kwanyee Leung, Ph.D.,, Tongqing Zhou, Ph.D.,, I-Ting Teng, Ph.D.,, Alicia Widge, M.D.,, Ingelise Gordon, M.A.,, Laura Novik, R.N.,, Rebecca A. Gillespie, B.S.,, Rebecca J. Loomis, Ph.D.,, Juan I. Moliva, Ph.D.,, Guillaume Stewart-Jones, Ph.D.,, Sunny Himansu, M.B.,, Wing-Pui Kong, Ph.D.,, Martha C. Nason, Ph.D.,, Kaitlyn M. Morabito, Ph.D.,, Tracy J. Ruckwardt, Ph.D.,, Julie E. Ledgerwood, D.O.,, Martin R. Gaudinski, M.D.,, Peter D. Kwong, Ph.D.,, John R. Mascola, M.D.,, Andrea Carfi, Ph.D.,, Mark G. Lewis, Ph.D.,, Ralph S. Baric, Ph.D.,, Adrian McDermott, Ph.D.,, Ian N. Moore, D.V.M.,, Nancy J. Sullivan, Ph.D.,, Mario Roederer, Ph.D.,, Robert A. Seder, M.D.,, and Barney S. Graham, M.D.

Issue&Volume: 2020-07-28

Abstract:

BACKGROUND

Vaccines 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.

METHODS

Nonhuman primates received 10 or 100 μg 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.

RESULTS

The 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-μg dose group and 3481 in the 100-μg 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-μg 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.

CONCLUSIONS

Vaccination 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.

DOI: 10.1056/NEJMoa2024671

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2024671