一种基于安卡拉痘苗病毒载体的改良疫苗可保护猕猴免受严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染、免疫病理损伤及肺部功能障碍。
A modified vaccinia Ankara vector-based vaccine protects macaques from SARS-CoV-2 infection, immune pathology, and dysfunction in the lungs.
作者信息
Routhu Nanda Kishore, Cheedarla Narayanaiah, Gangadhara Sailaja, Bollimpelli Venkata Satish, Boddapati Arun K, Shiferaw Ayalnesh, Rahman Sheikh Abdul, Sahoo Anusmita, Edara Venkata Viswanadh, Lai Lilin, Floyd Katharine, Wang Shelly, Fischinger Stephanie, Atyeo Caroline, Shin Sally A, Gumber Sanjeev, Kirejczyk Shannon, Cohen Joyce, Jean Sherrie M, Wood Jennifer S, Connor-Stroud Fawn, Stammen Rachelle L, Upadhyay Amit A, Pellegrini Kathryn, Montefiori David, Shi Pei-Yong, Menachery Vineet D, Alter Galit, Vanderford Thomas H, Bosinger Steven E, Suthar Mehul S, Amara Rama Rao
机构信息
Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Microbiology and Immunology, Emory School of Medicine, Emory University, Atlanta, GA 30322, USA.
Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Pathology, Emory School of Medicine, Emory University, Atlanta, GA 30322, USA.
出版信息
Immunity. 2021 Mar 9;54(3):542-556.e9. doi: 10.1016/j.immuni.2021.02.001. Epub 2021 Feb 4.
A combination of vaccination approaches will likely be necessary to fully control the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Here, we show that modified vaccinia Ankara (MVA) vectors expressing membrane-anchored pre-fusion stabilized spike (MVA/S) but not secreted S1 induced strong neutralizing antibody responses against SARS-CoV-2 in mice. In macaques, the MVA/S vaccination induced strong neutralizing antibodies and CD8 T cell responses, and conferred protection from SARS-CoV-2 infection and virus replication in the lungs as early as day 2 following intranasal and intratracheal challenge. Single-cell RNA sequencing analysis of lung cells on day 4 after infection revealed that MVA/S vaccination also protected macaques from infection-induced inflammation and B cell abnormalities and lowered induction of interferon-stimulated genes. These results demonstrate that MVA/S vaccination induces neutralizing antibodies and CD8 T cells in the blood and lungs and is a potential vaccine candidate for SARS-CoV-2.
可能需要多种疫苗接种方法相结合，才能全面控制严重急性呼吸综合征冠状病毒2（SARS-CoV-2）大流行。在此，我们表明，表达膜锚定预融合稳定刺突蛋白的改良安卡拉痘苗病毒（MVA）载体（MVA/S），而非分泌型S1，可在小鼠体内诱导针对SARS-CoV-2的强烈中和抗体反应。在猕猴中，MVA/S疫苗接种诱导了强烈的中和抗体和CD8 T细胞反应，并在鼻内和气管内攻击后第2天就对肺部的SARS-CoV-2感染和病毒复制提供了保护。感染后第4天对肺细胞进行的单细胞RNA测序分析表明，MVA/S疫苗接种还保护猕猴免受感染诱导的炎症和B细胞异常影响，并降低了干扰素刺激基因的诱导。这些结果表明，MVA/S疫苗接种可在血液和肺部诱导中和抗体和CD8 T细胞，是一种潜在的SARS-CoV-2疫苗候选物。
Zotero 插件