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

IF 3.9 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Scientific Reports Pub Date : 2025-07-26 DOI:10.1038/s41598-025-12320-z

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

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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.

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SARS-CoV-2 mRNA疫苗在饮食诱导的肥胖小鼠中具有保护作用，尽管肺部免疫细胞谱发生了改变。

高血压、糖尿病和肥胖是影响COVID-19重症病例的合并症，并与接种疫苗后体液免疫力低下有关。我们假设饮食性肥胖（DIO） K18-hACE2小鼠模型可以用来揭示对COVID-19免疫反应的性别和DIO特异性差异。为了验证这一假设，我们用COVID-19 mRNA疫苗免疫雄性和雌性DIO小鼠。雌性DIO小鼠免疫后表现出比雄性DIO小鼠更高的识别SARS-CoV-2变异RBD的中和抗体水平。在Omicron SARS-CoV-2攻毒后，肺组织单细胞RNA测序分析表明，免疫后的DIO小鼠naïve B细胞数量减少，雌性DIO小鼠接种后巨噬细胞数量增加。病毒负荷分析显示，DIO变量不影响免疫小鼠的免疫力。总体而言，本研究强调了COVID-19 mRNA疫苗在合并症SARS-CoV-2小鼠攻击模型中具有保护作用的能力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Scientific Reports Natural Science Disciplines-

CiteScore

7.50

自引率

4.30%

发文量

19567

审稿时长

3.9 months

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