Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Science. 2021 Sep 17;373(6561):eabj0299. doi: 10.1126/science.abj0299.
Immune correlates of protection can be used as surrogate endpoints for vaccine efficacy. Here, nonhuman primates (NHPs) received either no vaccine or doses ranging from 0.3 to 100 μg of the mRNA-1273 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. mRNA-1273 vaccination elicited circulating and mucosal antibody responses in a dose-dependent manner. Viral replication was significantly reduced in bronchoalveolar lavages and nasal swabs after SARS-CoV-2 challenge in vaccinated animals and most strongly correlated with levels of anti–S antibody and neutralizing activity. Lower antibody levels were needed for reduction of viral replication in the lower airway than in the upper airway. Passive transfer of mRNA-1273–induced immunoglobulin G to naïve hamsters was sufficient to mediate protection. Thus, mRNA-1273 vaccine–induced humoral immune responses are a mechanistic correlate of protection against SARS-CoV-2 in NHPs.
免疫相关性可作为疫苗效力的替代终点。在这项研究中，非人类灵长类动物（NHPs）接受了未接种疫苗或 0.3 至 100μg 剂量的 mRNA-1273 严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）疫苗。mRNA-1273 疫苗接种以剂量依赖的方式引起循环和粘膜抗体反应。在接种疫苗的动物中，SARS-CoV-2 攻击后，支气管肺泡灌洗液和鼻拭子中的病毒复制明显减少，与抗-S 抗体和中和活性水平的相关性最强。与上呼吸道相比，下呼吸道需要更低的抗体水平才能减少病毒复制。将 mRNA-1273 诱导的免疫球蛋白 G 被动转移给无经验的仓鼠足以介导保护。因此，mRNA-1273 疫苗诱导的体液免疫反应是非人类灵长类动物中针对 SARS-CoV-2 的保护机制相关性。
