COVID-19 vaccine mRNA-1273 elicits a protective immune profile in mice that is not associated with vaccine-enhanced disease upon SARS-CoV-2 challenge.
COVID-19 vaccine mRNA-1273 elicits a protective immune profile in mice that is not associated with vaccine-enhanced disease upon SARS-CoV-2 challenge.
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COVID-19 疫苗 mRNA-1273 在小鼠体内引发保护性免疫特征，该免疫特征与 SARS-CoV-2 攻击后疫苗增强的疾病无关。
DOI：
10.1016/j.immuni.2021.06.018
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发表时间：
2021-08-10
期刊：
影响因子：
32.4
通讯作者：
Ruckwardt TJ
中科院分区：
文献类型：
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作者：
DiPiazza AT;Leist SR;Abiona OM;Moliva JI;Werner A;Minai M;Nagata BM;Bock KW;Phung E;Schäfer A;Dinnon KH 3rd;Chang LA;Loomis RJ;Boyoglu-Barnum S;Alvarado GS;Sullivan NJ;Edwards DK;Morabito KM;Mascola JR;Carfi A;Corbett KS;Moore IN;Baric RS;Graham BS;Ruckwardt TJ
先前在严重急性呼吸综合征（SARS）和MERS冠状病毒疫苗的一些临床前模型中观察到了疫苗相关增强型呼吸道疾病（VAERD）。我们使用SARS冠状病毒2（SARS-CoV-2）小鼠适应的第10代致死性攻击病毒（MA 10）急性肺损伤小鼠模型，以评估研究级mRNA-1273接种动物的免疫应答和免疫病理学的潜力。与盐水免疫的动物相比，全灭活病毒或热变性刺突蛋白亚单位疫苗与设计用于引发低效力抗体和Th 2偏斜的CD 4 + T细胞导致病毒滴度降低和攻击后体重减轻，但肺中的病理变化更严重。相比之下，保护剂量的mRNA-1273诱导有利的体液和细胞免疫应答，其在攻击时保护上呼吸道和下呼吸道免受病毒复制。与给予生理盐水的动物相比，亚保护剂量的mRNA-1273减少了病毒复制和有限的组织病理学表现。总的来说，我们的研究结果表明，免疫学特征与抗病毒保护相关，而不会在接种mRNA-1273后增强疾病。由于此前已观察到疫苗增强呼吸道病毒的疾病，因此必须在临床前动物模型中对COVID-19疫苗进行全面的安全性评估。在这里，迪皮亚扎和莱斯特等人。提供了在用研究级mRNA-1273免疫的小鼠中SARS-CoV-2攻击后没有肺部疾病的情况下抗病毒保护的证据。
Vaccine-associated enhanced respiratory disease (VAERD) was previously observed in some preclinical models of severe acute respiratory syndrome (SARS) and MERS coronavirus vaccines. We used the SARS coronavirus 2 (SARS-CoV-2) mouse-adapted, passage 10, lethal challenge virus (MA10) mouse model of acute lung injury to evaluate the immune response and potential for immunopathology in animals vaccinated with research-grade mRNA-1273. Whole-inactivated virus or heat-denatured spike protein subunit vaccines with alum designed to elicit low-potency antibodies and Th2-skewed CD4+ T cells resulted in reduced viral titers and weight loss post challenge but more severe pathological changes in the lung compared to saline-immunized animals. In contrast, a protective dose of mRNA-1273 induced favorable humoral and cellular immune responses that protected from viral replication in the upper and lower respiratory tract upon challenge. A subprotective dose of mRNA-1273 reduced viral replication and limited histopathological manifestations compared to animals given saline. Overall, our findings demonstrate an immunological signature associated with antiviral protection without disease enhancement following vaccination with mRNA-1273. As vaccine-enhanced disease to respiratory viruses has been previously observed, a thorough safety evaluation of COVID-19 vaccines in preclinical animal models is essential. Here, DiPiazza and Leist et al. provide evidence for antiviral protection in the absence of lung disease following SARS-CoV-2 challenge in mice immunized with research-grade mRNA-1273.
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DOI：
10.1056/nejmoa2029849
发表时间：
2021-01-21
期刊：
The New England journal of medicine
影响因子：
--
作者：
Chen P;Nirula A;Heller B;Gottlieb RL;Boscia J;Morris J;Huhn G;Cardona J;Mocherla B;Stosor V;Shawa I;Adams AC;Van Naarden J;Custer KL;Shen L;Durante M;Oakley G;Schade AE;Sabo J;Patel DR;Klekotka P;Skovronsky DM;BLAZE-1 Investigators
通讯作者：
BLAZE-1 Investigators
影响因子：
100.3
作者：
Chen, Zeyu;John Wherry, E.
通讯作者：
John Wherry, E.
DOI：
10.1056/nejmoa2035389
发表时间：
2021-02-04
期刊：
The New England journal of medicine
影响因子：
--
作者：
Baden LR;El Sahly HM;Essink B;Kotloff K;Frey S;Novak R;Diemert D;Spector SA;Rouphael N;Creech CB;McGettigan J;Khetan S;Segall N;Solis J;Brosz A;Fierro C;Schwartz H;Neuzil K;Corey L;Gilbert P;Janes H;Follmann D;Marovich M;Mascola J;Polakowski L;Ledgerwood J;Graham BS;Bennett H;Pajon R;Knightly C;Leav B;Deng W;Zhou H;Han S;Ivarsson M;Miller J;Zaks T;COVE Study Group
通讯作者：
COVE Study Group
影响因子：
32.4
作者：
Jarjour NN;Masopust D;Jameson SC
通讯作者：
Jameson SC
影响因子：
64.8
作者：
Arvin, Ann M.;Fink, Katja;Virgin, Herbert W.
通讯作者：
Virgin, Herbert W.