EBioMedicine · 2023
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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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
Аннотация
BACKGROUND: 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.
METHODS: 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.
FINDINGS: 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.
INTERPRETATION: 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.
FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.
METHODS: 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.
FINDINGS: 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.
INTERPRETATION: 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.
FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.