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Immune correlates of protection by mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates
Science ( IF 44.7 ) Pub Date : 2021-07-29 , DOI: 10.1126/science.abj0299 Kizzmekia S Corbett 1 , Martha C Nason 2 , Britta Flach 1 , Matthew Gagne 1 , Sarah O'Connell 1 , Timothy S Johnston 1 , Shruti N Shah 1 , Venkata Viswanadh Edara 3 , Katharine Floyd 3 , Lilin Lai 3 , Charlene McDanal 4 , Joseph R Francica 1 , Barbara Flynn 1 , Kai Wu 5 , Angela Choi 5 , Matthew Koch 5 , Olubukola M Abiona 1 , Anne P Werner 1 , Juan I Moliva 1 , Shayne F Andrew 1 , Mitzi M Donaldson 1 , Jonathan Fintzi 1 , Dillon R Flebbe 1 , Evan Lamb 1 , Amy T Noe 1 , Saule T Nurmukhambetova 1 , Samantha J Provost 1 , Anthony Cook 6 , Alan Dodson 6 , Andrew Faudree 6 , Jack Greenhouse 6 , Swagata Kar 6 , Laurent Pessaint 6 , Maciel Porto 6 , Katelyn Steingrebe 6 , Daniel Valentin 6 , Serge Zouantcha 6 , Kevin W Bock 7 , Mahnaz Minai 7 , Bianca M Nagata 7 , Renee van de Wetering 1 , Seyhan Boyoglu-Barnum 1 , Kwanyee Leung 1 , Wei Shi 1 , Eun Sung Yang 1 , Yi Zhang 1 , John-Paul M Todd 1 , Lingshu Wang 1 , Gabriela S Alvarado 1 , Hanne Andersen 6 , Kathryn E Foulds 1 , Darin K Edwards 5 , John R Mascola 1 , Ian N Moore 7 , Mark G Lewis 6 , Andrea Carfi 5 , David Montefiori 4 , Mehul S Suthar 3, 8 , Adrian McDermott 1 , Mario Roederer 1 , Nancy J Sullivan 1 , Daniel C Douek 1 , Barney S Graham 1 , Robert A Seder 1
Science ( IF 44.7 ) Pub Date : 2021-07-29 , DOI: 10.1126/science.abj0299 Kizzmekia S Corbett 1 , Martha C Nason 2 , Britta Flach 1 , Matthew Gagne 1 , Sarah O'Connell 1 , Timothy S Johnston 1 , Shruti N Shah 1 , Venkata Viswanadh Edara 3 , Katharine Floyd 3 , Lilin Lai 3 , Charlene McDanal 4 , Joseph R Francica 1 , Barbara Flynn 1 , Kai Wu 5 , Angela Choi 5 , Matthew Koch 5 , Olubukola M Abiona 1 , Anne P Werner 1 , Juan I Moliva 1 , Shayne F Andrew 1 , Mitzi M Donaldson 1 , Jonathan Fintzi 1 , Dillon R Flebbe 1 , Evan Lamb 1 , Amy T Noe 1 , Saule T Nurmukhambetova 1 , Samantha J Provost 1 , Anthony Cook 6 , Alan Dodson 6 , Andrew Faudree 6 , Jack Greenhouse 6 , Swagata Kar 6 , Laurent Pessaint 6 , Maciel Porto 6 , Katelyn Steingrebe 6 , Daniel Valentin 6 , Serge Zouantcha 6 , Kevin W Bock 7 , Mahnaz Minai 7 , Bianca M Nagata 7 , Renee van de Wetering 1 , Seyhan Boyoglu-Barnum 1 , Kwanyee Leung 1 , Wei Shi 1 , Eun Sung Yang 1 , Yi Zhang 1 , John-Paul M Todd 1 , Lingshu Wang 1 , Gabriela S Alvarado 1 , Hanne Andersen 6 , Kathryn E Foulds 1 , Darin K Edwards 5 , John R Mascola 1 , Ian N Moore 7 , Mark G Lewis 6 , Andrea Carfi 5 , David Montefiori 4 , Mehul S Suthar 3, 8 , Adrian McDermott 1 , Mario Roederer 1 , Nancy J Sullivan 1 , Daniel C Douek 1 , Barney S Graham 1 , Robert A Seder 1
Affiliation
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 SARS-CoV-2 vaccine, mRNA-1273. 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 most strongly correlated with levels of anti-S antibody and neutralizing activity. Lower antibody levels are needed for reduction of viral replication in the lower airway than in the upper airway. Passive transfer of mRNA-1273-induced IgG 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.
中文翻译：
非人灵长类动物中 mRNA-1273 疫苗针对 SARS-CoV-2 的保护作用的免疫相关性
保护的免疫相关性可用作疫苗功效的替代终点。在这里，非人灵长类动物 (NHP) 要么不接种疫苗，要么接种剂量范围为 0.3 至 100 μg 的 SARS-CoV-2 疫苗 mRNA-1273。mRNA-1273 疫苗接种以剂量依赖性方式引发强烈的循环和粘膜抗体反应。接种疫苗的动物受到 SARS-CoV-2 攻击后，支气管肺泡灌洗液和鼻拭子中的病毒复制显着减少，并且与抗 S 抗体和中和活性水平密切相关。与上呼吸道相比，下呼吸道中减少病毒复制所需的抗体水平较低。将 mRNA-1273 诱导的 IgG 被动转移至未接触过的仓鼠体内足以介导保护作用。因此，mRNA-1273 疫苗诱导的体液免疫反应与 NHP 中针对 SARS-CoV-2 的保护机制相关。
更新日期：2021-09-10
中文翻译：
非人灵长类动物中 mRNA-1273 疫苗针对 SARS-CoV-2 的保护作用的免疫相关性
保护的免疫相关性可用作疫苗功效的替代终点。在这里，非人灵长类动物 (NHP) 要么不接种疫苗，要么接种剂量范围为 0.3 至 100 μg 的 SARS-CoV-2 疫苗 mRNA-1273。mRNA-1273 疫苗接种以剂量依赖性方式引发强烈的循环和粘膜抗体反应。接种疫苗的动物受到 SARS-CoV-2 攻击后，支气管肺泡灌洗液和鼻拭子中的病毒复制显着减少，并且与抗 S 抗体和中和活性水平密切相关。与上呼吸道相比，下呼吸道中减少病毒复制所需的抗体水平较低。将 mRNA-1273 诱导的 IgG 被动转移至未接触过的仓鼠体内足以介导保护作用。因此，mRNA-1273 疫苗诱导的体液免疫反应与 NHP 中针对 SARS-CoV-2 的保护机制相关。
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