非人灵长类动物中mRNA-1273免疫接种对SARS-CoV-2感染的保护作用的免疫相关因素

Immune Correlates of Protection by mRNA-1273 Immunization against SARS-CoV-2 Infection in Nonhuman Primates.

作者信息

Corbett Kizzmekia S, Nason Martha C, Flach Britta, Gagne Matthew, O' Connell Sarah, Johnston Timothy S, Shah Shruti N, Edara Venkata Viswanadh, Floyd Katharine, Lai Lilin, McDanal Charlene, Francica Joseph R, Flynn Barbara, Wu Kai, Choi Angela, Koch Matthew, Abiona Olubukola M, Werner Anne P, Alvarado Gabriela S, Andrew Shayne F, Donaldson Mitzi M, Fintzi Jonathan, Flebbe Dillon R, Lamb Evan, Noe Amy T, Nurmukhambetova Saule T, Provost Samantha J, Cook Anthony, Dodson Alan, Faudree Andrew, Greenhouse Jack, Kar Swagata, Pessaint Laurent, Porto Maciel, Steingrebe Katelyn, Valentin Daniel, Zouantcha Serge, Bock Kevin W, Minai Mahnaz, Nagata Bianca M, Moliva Juan I, van de Wetering Renee, Boyoglu-Barnum Seyhan, Leung Kwanyee, Shi Wei, Yang Eun Sung, Zhang Yi, Todd John-Paul M, Wang Lingshu, Andersen Hanne, Foulds Kathryn E, Edwards Darin K, Mascola John R, Moore Ian N, Lewis Mark G, Carfi Andrea, Montefiori David, Suthar Mehul S, McDermott Adrian, Sullivan Nancy J, Roederer Mario, Douek Daniel C, Graham Barney S, Seder Robert A

出版信息

bioRxiv. 2021 Apr 23:2021.04.20.440647. doi: 10.1101/2021.04.20.440647.

DOI:10.1101/2021.04.20.440647

PMID:33907752

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8077626/

Abstract

UNLABELLED

Immune correlates of protection can be used as surrogate endpoints for vaccine efficacy. The nonhuman primate (NHP) model of SARS-CoV-2 infection replicates key features of human infection and may be used to define immune correlates of protection following vaccination. Here, NHP received either no vaccine or doses ranging from 0.3 - 100 μg of mRNA-1273, a mRNA vaccine encoding the prefusion-stabilized SARS-CoV-2 spike (S-2P) protein encapsulated in a lipid nanoparticle. mRNA-1273 vaccination elicited robust circulating and mucosal antibody responses in a dose-dependent manner. Viral replication was significantly reduced in bronchoalveolar lavages and nasal swabs following SARS-CoV-2 challenge in vaccinated animals and was most strongly correlated with levels of anti-S antibody binding and neutralizing activity. Consistent with antibodies being a correlate of protection, passive transfer of vaccine-induced IgG to naïve hamsters was sufficient to mediate protection. Taken together, these data show that mRNA-1273 vaccine-induced humoral immune responses are a mechanistic correlate of protection against SARS-CoV-2 infection in NHP.

ONE-SENTENCE SUMMARY: mRNA-1273 vaccine-induced antibody responses are a mechanistic correlate of protection against SARS-CoV-2 infection in NHP.

摘要

未标记

保护性免疫相关指标可作为疫苗效力的替代终点。严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染的非人灵长类动物（NHP）模型可复制人类感染的关键特征，可用于确定接种疫苗后的保护性免疫相关指标。在此，NHP要么未接种疫苗，要么接种了剂量范围为0.3 - 100μg的mRNA-1273，这是一种mRNA疫苗，编码封装在脂质纳米颗粒中的预融合稳定化SARS-CoV-2刺突（S-2P）蛋白。mRNA-1273接种以剂量依赖方式引发了强劲的循环和黏膜抗体反应。在接种疫苗的动物受到SARS-CoV-2攻击后，支气管肺泡灌洗和鼻拭子中的病毒复制显著减少，且与抗S抗体结合水平和中和活性最密切相关。与抗体作为保护性相关指标一致，将疫苗诱导的IgG被动转移至未接触过病毒的仓鼠足以介导保护作用。综上所述，这些数据表明，mRNA-1273疫苗诱导的体液免疫反应是NHP针对SARS-CoV-2感染的保护性机制相关指标。