SARS-CoV-2 mRNA vaccines confer protection in diet-induced obese mice despite altered immune cell profiles in the lung
Abstract 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 difference...
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| Format: | Article |
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Nature Portfolio
2025-07-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-12320-z |
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| author | Katherine S. Lee Dylan T. Boehm Olivia A. Miller-Stump Nathaniel A. Rader Melissa Cooper Holly A. Cyphert Emel Sen-Kilic Mariette Barbier F. Heath Damron |
| author_facet | Katherine S. Lee Dylan T. Boehm Olivia A. Miller-Stump Nathaniel A. Rader Melissa Cooper Holly A. Cyphert Emel Sen-Kilic Mariette Barbier F. Heath Damron |
| author_sort | Katherine S. Lee |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-f0e40b82885d4e038babfbb12a2d52d0 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-f0e40b82885d4e038babfbb12a2d52d02025-08-20T03:46:00ZengNature PortfolioScientific Reports2045-23222025-07-0115111310.1038/s41598-025-12320-zSARS-CoV-2 mRNA vaccines confer protection in diet-induced obese mice despite altered immune cell profiles in the lungKatherine S. Lee0Dylan T. Boehm1Olivia A. Miller-Stump2Nathaniel A. Rader3Melissa Cooper4Holly A. Cyphert5Emel Sen-Kilic6Mariette Barbier7F. Heath Damron8Department of Microbiology, Immunology, and Cell Biology, West Virginia UniversityDepartment of Microbiology, Immunology, and Cell Biology, West Virginia UniversityDepartment of Microbiology, Immunology, and Cell Biology, West Virginia UniversityDepartment of Microbiology, Immunology, and Cell Biology, West Virginia UniversityDepartment of Microbiology, Immunology, and Cell Biology, West Virginia UniversityDepartment of Biological Sciences, Marshall UniversityDepartment of Microbiology, Immunology, and Cell Biology, West Virginia UniversityDepartment of Microbiology, Immunology, and Cell Biology, West Virginia UniversityDepartment of Microbiology, Immunology, and Cell Biology, West Virginia UniversityAbstract 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.https://doi.org/10.1038/s41598-025-12320-zSARS-CoV-2COVID-19DiabetesObesityK18-hACE2 transgenic mouseOmicron variant |
| spellingShingle | Katherine S. Lee Dylan T. Boehm Olivia A. Miller-Stump Nathaniel A. Rader Melissa Cooper Holly A. Cyphert Emel Sen-Kilic Mariette Barbier F. Heath Damron SARS-CoV-2 mRNA vaccines confer protection in diet-induced obese mice despite altered immune cell profiles in the lung Scientific Reports SARS-CoV-2 COVID-19 Diabetes Obesity K18-hACE2 transgenic mouse Omicron variant |
| title | SARS-CoV-2 mRNA vaccines confer protection in diet-induced obese mice despite altered immune cell profiles in the lung |
| title_full | SARS-CoV-2 mRNA vaccines confer protection in diet-induced obese mice despite altered immune cell profiles in the lung |
| title_fullStr | SARS-CoV-2 mRNA vaccines confer protection in diet-induced obese mice despite altered immune cell profiles in the lung |
| title_full_unstemmed | SARS-CoV-2 mRNA vaccines confer protection in diet-induced obese mice despite altered immune cell profiles in the lung |
| title_short | SARS-CoV-2 mRNA vaccines confer protection in diet-induced obese mice despite altered immune cell profiles in the lung |
| title_sort | sars cov 2 mrna vaccines confer protection in diet induced obese mice despite altered immune cell profiles in the lung |
| topic | SARS-CoV-2 COVID-19 Diabetes Obesity K18-hACE2 transgenic mouse Omicron variant |
| url | https://doi.org/10.1038/s41598-025-12320-z |
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