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mRNA-1273 protects against SARS-CoV-2 beta infection in nonhuman primates
Nature Immunology ( IF 27.7 ) Pub Date : 2021-08-20 , DOI: 10.1038/s41590-021-01021-0
Kizzmekia S Corbett 1, 2 , Anne P Werner 1 , Sarah O' Connell 1 , Matthew Gagne 1 , Lilin Lai 3 , Juan I Moliva 1 , Barbara Flynn 1 , Angela Choi 4 , Matthew Koch 4 , Kathryn E Foulds 1 , Shayne F Andrew 1 , Dillon R Flebbe 1 , Evan Lamb 1 , Saule T Nurmukhambetova 1 , Samantha J Provost 1 , Kevin W Bock 5 , Mahnaz Minai 5 , Bianca M Nagata 5 , Alex Van Ry 6 , Zackery Flinchbaugh 6 , Timothy S Johnston 1 , Elham Bayat Mokhtari 1 , Prakriti Mudvari 1 , Amy R Henry 1 , Farida Laboune 1 , Becky Chang 6 , Maciel Porto 6 , Jaclyn Wear 6 , Gabriela S Alvarado 1 , Seyhan Boyoglu-Barnum 1 , John-Paul M Todd 1 , Bridget Bart 6 , Anthony Cook 6 , Alan Dodson 6 , Laurent Pessaint 6 , Katelyn Steingrebe 6 , Sayda Elbashir 4 , Manjari Sriparna 1 , Andrew Pekosz 7 , Hanne Andersen 6 , Kai Wu 4 , Darin K Edwards 4 , Swagata Kar 6 , Mark G Lewis 6 , Eli Boritz 1 , Ian N Moore 5 , Andrea Carfi 4 , Mehul S Suthar 3, 8 , Adrian McDermott 1 , Mario Roederer 1 , Martha C Nason 9 , Nancy J Sullivan 1 , Daniel C Douek 1 , Barney S Graham 1 , Robert A Seder 1
Affiliation  

B.1.351 is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant most resistant to antibody neutralization. We demonstrate how the dose and number of immunizations influence protection. Nonhuman primates received two doses of 30 or 100 µg of Moderna’s mRNA-1273 vaccine, a single immunization of 30 µg, or no vaccine. Two doses of 100 µg of mRNA-1273 induced 50% inhibitory reciprocal serum dilution neutralizing antibody titers against live SARS-CoV-2 p.Asp614Gly and B.1.351 of 3,300 and 240, respectively. Higher neutralizing responses against B.1.617.2 were also observed after two doses compared to a single dose. After challenge with B.1.351, there was ~4- to 5-log10 reduction of viral subgenomic RNA and low to undetectable replication in bronchoalveolar lavages in the two-dose vaccine groups, with a 1-log10 reduction in nasal swabs in the 100-µg group. These data establish that a two-dose regimen of mRNA-1273 will be critical for providing upper and lower airway protection against major variants of concern.



中文翻译:

mRNA-1273 可防止非人灵长类动物感染 SARS-CoV-2 beta

B.1.351 是对抗体中和最具抵抗力的严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 变种。我们展示了免疫接种的剂量和次数如何影响保护。非人类灵长类动物接受两剂 30 或 100 µg 的 Moderna mRNA-1273 疫苗,单次免疫 30 µg,或不接种疫苗。两剂 100 µg mRNA-1273 诱导针对活 SARS-CoV-2 p.Asp614Gly 和 B.1.351 的 50% 抑制性血清稀释倒数中和抗体滴度分别为 3,300 和 240。与单次剂量相比,两次剂量后还观察到针对 B.1.617.2 的更高中和反应。用 B.1.351 攻击后,两剂疫苗组中病毒亚基因组 RNA 减少约4-5-log 10 ,支气管肺泡灌洗液中的复制量低至不可检测,而鼻拭子中的鼻拭子减少了1-log 10 。 100 µg 组。这些数据表明,mRNA-1273 的两剂量方案对于提供上呼吸道和下呼吸道保护以抵御主要的主要变异至关重要。

更新日期:2021-08-20
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