COVID-19 mRNA vaccine protects against SARS-CoV-2 Omicron BA.1 infection in diet-induced obese mice through boosting host innate antiviral responses.
COVID-19 mRNA vaccine protects against SARS-CoV-2 Omicron BA.1 infection in diet-induced obese mice through boosting host innate antiviral responses.
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DOI：
10.1016/j.ebiom.2023.104485
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发表时间：
2023-03
期刊：
影响因子：
11.1
通讯作者：
Chu, Hin
中科院分区：
文献类型：
--
作者：
Chen, Yanxia;Song, Wenchen;Li, Can;Wang, Jiaxuan;Liu, Feifei;Ye, Zhanhong;Ren, Peidi;Tong, Yihan;Li, Junhua;Ou, Zhihua;Lee, Andrew Chak-Yiu;Cai, Jian-Piao;Wong, Bosco Ho-Yin;Chan, Jasper Fuk-Woo;Yuen, Kwok-Yung;Zhang, AnnaJin-Xia;Chu, Hin
肥胖是一种全球性流行病，被认为是2019冠状病毒病（COVID-19）严重表现的危险因素。严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）的致病性以及肥胖个体对感染、再感染和疫苗接种的反应仍不完全清楚。采用饮食性肥胖（DIO）小鼠模型，研究了SARS-CoV-2 α -和Omicron ba .1诱导的疾病表现和宿主对感染、再感染和COVID-19 mRNA疫苗接种的免疫反应。与瘦小鼠不同，Omicron BA.1和α在DIO小鼠的肺中复制到相当水平，并导致相似程度的组织损伤。重要的是，在DIO小鼠中，T细胞和B细胞介导的对SARS-CoV-2感染或COVID-19 mRNA接种的适应性免疫应答均受损，导致再感染倾向增加，疫苗效力降低。然而，尽管缺乏中和抗体，接种的DIO小鼠在Omicron攻击时可以保护肺免受损伤，同时肺组织中产生更多的IFN-α和IFN-β。肺部RNAseq和随后的实验表明，与未接种疫苗的对照组相比，DIO小鼠接种COVID-19 mRNA增强了抗病毒先天免疫反应，包括IFN-α的表达。我们的研究结果表明，COVID-19 mRNA疫苗接种增强了肥胖小鼠的先天抗病毒反应，在一定程度上保护了适应性免疫不理想的DIO小鼠。资助本研究的机构的完整列表可以在致谢部分找到。
Obesity is a worldwide epidemic and is considered a risk factor of severe manifestation of Coronavirus Disease 2019 (COVID-19). The pathogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and host responses to infection, re-infection, and vaccination in individuals with obesity remain incompletely understood. Using the diet-induced obese (DIO) mouse model, we studied SARS-CoV-2 Alpha- and Omicron BA.1-induced disease manifestations and host immune responses to infection, re-infection, and COVID-19 mRNA vaccination. Unlike in lean mice, Omicron BA.1 and Alpha replicated to comparable levels in the lungs of DIO mice and resulted in similar degree of tissue damages. Importantly, both T cell and B cell mediated adaptive immune responses to SARS-CoV-2 infection or COVID-19 mRNA vaccination are impaired in DIO mice, leading to higher propensity of re-infection and lower vaccine efficacy. However, despite the absence of neutralizing antibody, vaccinated DIO mice are protected from lung damage upon Omicron challenge, accompanied with significantly more IFN-α and IFN-β production in the lung tissue. Lung RNAseq and subsequent experiments indicated that COVID-19 mRNA vaccination in DIO mice boosted antiviral innate immune response, including the expression of IFN-α, when compared to the nonvaccinated controls. Our findings suggested that COVID-19 mRNA vaccination enhances host innate antiviral responses in obesity which protect the DIO mice to a certain degree when adaptive immunity is suboptimal. A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.
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影响因子：
30.3
作者：
Achkar JM;Casadevall A
通讯作者：
Casadevall A
影响因子：
11.1
作者：
Alu A;Chen L;Lei H;Wei Y;Tian X;Wei X
通讯作者：
Wei X
DOI：
10.1126/science.abc4730
发表时间：
2020-09-25
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
Gu H;Chen Q;Yang G;He L;Fan H;Deng YQ;Wang Y;Teng Y;Zhao Z;Cui Y;Li Y;Li XF;Li J;Zhang NN;Yang X;Chen S;Guo Y;Zhao G;Wang X;Luo DY;Wang H;Yang X;Li Y;Han G;He Y;Zhou X;Geng S;Sheng X;Jiang S;Sun S;Qin CF;Zhou Y
通讯作者：
Zhou Y
影响因子：
7.3
作者：
Hulme KD;Noye EC;Short KR;Labzin LI
通讯作者：
Labzin LI
DOI：
10.3390/v14092067
发表时间：
2022-09-17
期刊：
Viruses
影响因子：
--
作者：
Briand F;Sencio V;Robil C;Heumel S;Deruyter L;Machelart A;Barthelemy J;Bogard G;Hoffmann E;Infanti F;Domenig O;Chabrat A;Richard V;Prévot V;Nogueiras R;Wolowczuk I;Pinet F;Sulpice T;Trottein F
通讯作者：
Trottein F