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

tetano

Editor, Senior Moderator
EBioMedicine


. 2023 Feb 27;89:104485.
doi: 10.1016/j.ebiom.2023.104485. Online ahead of print.
COVID-19 mRNA vaccine protects against SARS-CoV-2 Omicron BA.1 infection in diet-induced obese mice through boosting host innate antiviral responses


Yanxia Chen[SUP] 1 [/SUP], Wenchen Song[SUP] 2 [/SUP], Can Li[SUP] 2 [/SUP], Jiaxuan Wang[SUP] 3 [/SUP], Feifei Liu[SUP] 1 [/SUP], Zhanhong Ye[SUP] 1 [/SUP], Peidi Ren[SUP] 3 [/SUP], Yihan Tong[SUP] 3 [/SUP], Junhua Li[SUP] 3 [/SUP], Zhihua Ou[SUP] 3 [/SUP], Andrew Chak-Yiu Lee[SUP] 2 [/SUP], Jian-Piao Cai[SUP] 1 [/SUP], Bosco Ho-Yin Wong[SUP] 2 [/SUP], Jasper Fuk-Woo Chan[SUP] 4 [/SUP], Kwok-Yung Yuen[SUP] 4 [/SUP], Anna Jin-Xia Zhang[SUP] 5 [/SUP], Hin Chu[SUP] 6 [/SUP]



Affiliations

Abstract

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.

Keywords: COVID-19; Diet-induced obese mouse; Obesity; Omicron; SARS-CoV-2; Vaccination.
 
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