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黏膜接种减毒活重组新冠病毒疫苗可保护非人灵长类动物免受新冠病毒感染。

Mucosal administration of a live attenuated recombinant COVID-19 vaccine protects nonhuman primates from SARS-CoV-2.

作者信息

Tioni Mariana F, Jordan Robert, Pena Angie Silva, Garg Aditya, Wu Danlu, Phan Shannon I, Weiss Christopher M, Cheng Xing, Greenhouse Jack, Orekov Tatyana, Valentin Daniel, Kar Swagata, Pessaint Laurent, Andersen Hanne, Stobart Christopher C, Bloodworth Melissa H, Stokes Peebles R, Liu Yang, Xie Xuping, Shi Pei-Yong, Moore Martin L, Tang Roderick S

机构信息

Meissa Vaccines Inc, Redwood City, CA, USA.

Bill & Melinda Gates Foundation, Seattle, WA, USA.

出版信息

NPJ Vaccines. 2022 Jul 29;7(1):85. doi: 10.1038/s41541-022-00509-6.

DOI:10.1038/s41541-022-00509-6
PMID:35906244
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9334537/
Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 global pandemic. SARS-CoV-2 is an enveloped RNA virus that relies on its trimeric surface glycoprotein spike for entry into host cells. Here we describe the COVID-19 vaccine candidate MV-014-212, a live, attenuated, recombinant human respiratory syncytial virus expressing a chimeric SARS-CoV-2 spike as the only viral envelope protein. MV-014-212 was attenuated and immunogenic in African green monkeys (AGMs). One mucosal administration of MV-014-212 in AGMs protected against SARS-CoV-2 challenge, reducing by more than 200-fold the peak shedding of SARS-CoV-2 in the nose. MV-014-212 elicited mucosal immunoglobulin A in the nose and neutralizing antibodies in serum that exhibited cross-neutralization against virus variants of concern Alpha, Beta, and Delta. Intranasally delivered, live attenuated vaccines such as MV-014-212 entail low-cost manufacturing suitable for global deployment. MV-014-212 is currently in Phase 1 clinical trials as an intranasal COVID-19 vaccine.

摘要

严重急性呼吸综合征冠状病毒2(SARS-CoV-2)是新冠疫情全球大流行的病原体。SARS-CoV-2是一种包膜RNA病毒,其进入宿主细胞依赖三聚体表面糖蛋白刺突。在此,我们描述了新冠疫苗候选株MV-014-212,这是一种减毒活重组人呼吸道合胞病毒,表达嵌合SARS-CoV-2刺突作为唯一的病毒包膜蛋白。MV-014-212在非洲绿猴(AGM)中具有减毒作用且具有免疫原性。在AGM中单次经黏膜给予MV-014-212可抵御SARS-CoV-2攻击,使鼻腔中SARS-CoV-2的峰值病毒载量降低200倍以上。MV-014-212可在鼻腔中诱导黏膜免疫球蛋白A,并在血清中诱导产生中和抗体,这些中和抗体对值得关注的病毒变体Alpha、Beta和Delta表现出交叉中和作用。像MV-014-212这样经鼻给药的减毒活疫苗生产成本低,适合全球推广。MV-014-212目前正作为一种经鼻新冠疫苗进行1期临床试验。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2692/9338042/d6287e8ab75f/41541_2022_509_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2692/9338042/1478d4307304/41541_2022_509_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2692/9338042/e45ffcbff034/41541_2022_509_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2692/9338042/0d95ae4006de/41541_2022_509_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2692/9338042/8862c1561253/41541_2022_509_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2692/9338042/d6287e8ab75f/41541_2022_509_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2692/9338042/1478d4307304/41541_2022_509_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2692/9338042/004456a38149/41541_2022_509_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2692/9338042/e45ffcbff034/41541_2022_509_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2692/9338042/0d95ae4006de/41541_2022_509_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2692/9338042/8862c1561253/41541_2022_509_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2692/9338042/d6287e8ab75f/41541_2022_509_Fig6_HTML.jpg

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