Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates
Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates
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DOI：
10.1056/nejmoa2024671
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发表时间：
2020-10-15
影响因子：
158.5
通讯作者：
Graham, Barney S.
中科院分区：
文献类型：
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作者：
Corbett, Kizzmekia S.;Flynn, Barbara;Graham, Barney S.
背景预防冠状病毒病2019年疫苗(新冠肺炎)是迫切需要的。非人灵长类动物接种SARS-CoV-2疫苗对上呼吸道和下呼吸道病毒复制的影响是非常重要的。方法非人灵长类动物接种10或100 mU g的RNA-1273，一种编码SARS-CoV-2融合蛋白的疫苗，或不接种疫苗。在用SARS-CoV-2攻击上、下呼吸道之前，评估抗体和T细胞反应。用聚合酶链式反应检测支气管肺泡灌洗液(BAL)和鼻拭子标本中病毒的活跃复制和基因组，并对肺组织标本进行组织病理学分析和病毒定量。结果mRNA1273候选疫苗诱导的抗体水平超过了恢复期血清，活病毒倒数50%抑制稀释度(ID50)几何平均滴度在10mU g组为501,100mU g组为3481。疫苗接种诱导1型辅助T细胞(Th1)偏向的CD4T细胞反应和低或检测不到的Th2或CD8T细胞反应。在两个免疫组中的8只动物中，有7只在攻击后第2天的BAL液中未检测到病毒复制。免疫后第2天，100 mU g剂量组的8只动物鼻腔内均未检测到病毒复制，两种疫苗组动物的肺部均未检测到炎症反应或病毒基因组或抗原的存在。结论非人灵长类动物的RNA-1273疫苗可诱导出较强的SARS-CoV-2中和活性，对上、下呼吸道有快速保护作用，肺组织未见病理改变。(由美国国立卫生研究院和其他机构资助。)两次注射编码SARS-CoV-2刺突蛋白的基于mRNA的疫苗在恒河猴中引起高水平的中和抗体和Th1CD4T细胞反应。在用鼻腔和气管内病毒免疫的动物攻击两天后，在支气管肺泡灌洗液和鼻分泌物中检测不到病毒复制。
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.