SARS-CoV-2 mRNA vaccines confer protection in diet-induced obese mice despite altered immune cell profiles in the lung

Hypertension, diabetes, and obesity are comorbidities that influence severe cases of COVID-19 and are associated with weak humoral immunity after vaccination. We hypothesized that the diet-induced obese (DIO) K18-hACE2 mouse model could be utilized to reveal sex and DIO- specific differences in responses to COVID-19 immunization. To test this hypothesis, we immunized male and female DIO mice with a COVID-19 mRNA vaccine. Female DIO mice after immunization showed higher neutralizing antibody levels that recognized both SARS-CoV-2 variant RBD than male DIO mice. After Omicron SARS-CoV-2 challenge, single cell RNA sequencing analysis of lung tissue suggested decreased naïve B cell populations in immunized DIO mice in addition to an increase in macrophages in vaccinated female DIO mice. Analysis of viral burden revealed that the DIO variable did not impact immunity in immunized mice. Overall, this study underscores the ability of COVID-19 mRNA vaccines to confer protection in the comorbid SARS-CoV-2 murine challenge model.