From the Vaccine Research Center (K.S.C., B. Flynn, K.E.F., J.R.F., S.B.-B., A.P.W., B. Flach, S. O'Connell, A.T.N., N.D., M.M.D., N.N.N., G.S.A., D.R.F., E.L., N.A.D.-R., B.C.L., M.K.L., S. O'Dell, S.D.S., E.P., L.A.C., C.Y., J.-P.M.T., W.S., Y.Z., O.M.A., L.W., A.P., E.S.Y., K.L., T.Z., I.-T.T., A.W., I.G., L.N., R.A.G., R.J.L., J.I.M., W.-P.K., K.M.M., T.J.R., J.E.L., M.R.G., P.D.K., J.R.M., A.M., N.J.S., M.R., R.A.S., B.S.G.), the Infectious Disease Pathogenesis Section (K.W.B., M.M., B.M.N., M.G.L.), and the Biostatistics Research Branch, Division of Clinical Research (M.C.N.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, and Bioqual (H.A., L.P., A.V.R., S.B., J.G., T.P.-T., A.S., T.-A.C., A. Cook, A.D., K.S., I.N.M.) and the Public Health Service Commissioned Corps (M.R.G.), Rockville - both in Maryland; the Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill (D.R.M., R.S.B.); Moderna, Cambridge, MA (D.K.E., G.S.-J., S.H., A. Carfi); and the Institute for Biomedical Sciences, George Washington University, Washington, DC (E.P.).
N Engl J Med. 2020 Oct 15;383(16):1544-1555. doi: 10.1056/NEJMoa2024671. Epub 2020 Jul 28.
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.
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.
The mRNA-1273 vaccine candidate induced antibody levels exceeding those in human convalescent-phase serum, with live-virus reciprocal 50% inhibitory dilution (ID) 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.
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. (Funded by the National Institutes of Health and others.).
急需预防 2019 年冠状病毒病（COVID-19）的疫苗。评估非人类灵长类动物中严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）疫苗对上下呼吸道病毒复制的影响很重要。
非人类灵长类动物接受了 10 或 100μg 的 mRNA-1273，这是一种编码 SARS-CoV-2 预融合稳定刺突蛋白的疫苗，或不接种疫苗。在上呼吸道和下呼吸道挑战 SARS-CoV-2 之前，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。
mRNA-1273 候选疫苗诱导的抗体水平超过了人类恢复期血清中的水平，在 10μg 剂量组中，活病毒 50%抑制稀释（ID）几何平均滴度为 501，在 100μg 剂量组中为 3481。接种疫苗诱导了 1 型辅助 T 细胞（Th1）偏向的 CD4 T 细胞反应，而 Th2 或 CD8 T 细胞反应较低或无法检测到。在挑战后第 2 天，两个疫苗组的八只动物中有七只在 BAL 液中未检测到病毒复制。在挑战后第 2 天，100μg 剂量组的八只动物中没有一只在鼻子中检测到病毒复制，并且在两个疫苗组的动物肺部中仅观察到有限的炎症或可检测到的病毒基因组或抗原。
在非人类灵长类动物中接种 mRNA-1273 可诱导出强大的 SARS-CoV-2 中和活性，在上呼吸道和下呼吸道迅速得到保护，并且肺部没有病理变化。（由美国国立卫生研究院等资助）。
