COVID-19 mRNA vaccine protects against SARS-CoV-2 Omicron BA.1 infection in diet-induced obese mice through boosting host innate antiviral responses

• Published in: EBioMedicine Vol. 89; p. 104485
• Main Authors: 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, Anna Jin-Xia, Chu, Hin
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2023; The Author(s). Published by Elsevier B.V
• Subjects: Animals; Antibodies, Neutralizing; Antibodies, Viral; Antiviral Agents; COVID-19; COVID-19 Vaccines; Diet; Diet-induced obese mouse; Humans; Interferon-alpha; Mice; Mice, Obese; mRNA Vaccines; Obesity; Omicron; Reinfection; RNA, Messenger; SARS-CoV-2; Vaccination; COVID-19; Obesity; Diet-induced obese mouse; SARS-CoV-2; Omicron; Vaccination
• ISSN: 2352-3964; 2352-3964
• DOI: 10.1016/j.ebiom.2023.104485

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.