免疫原性
医学
免疫学
胰岛素抵抗
免疫
免疫
人口
高胰岛素血症
肥胖
病毒学
免疫系统
内科学
环境卫生
作者
Timothy R. O’Meara,Etsuro Nanishi,Marisa E. McGrath,Soumik Barman,Danica Dong,Carly Dillen,Manisha Menon,Hyuk‐Soo Seo,Sirano Dhe‐Paganon,Robert K. Ernst,Ofer Levy,Matthew B. Frieman,David J. Dowling
标识
DOI:10.1016/j.jaci.2023.06.031
摘要
ABSTRACT
Background
Obesity and Type 2 Diabetes Mellitus (T2DM) are associated with an increased risk of severe outcomes from infectious diseases, including COVID-19. These conditions are also associated with distinct responses to immunization, including an impaired response to widely used SARS-CoV-2 mRNA vaccines. Objective
To establish a connection between reduced immunization efficacy via modeling the effects of metabolic diseases on vaccine immunogenicity that is essential for the development of more effective vaccines for this distinct vulnerable population. Methods
We utilized a murine model of diet-induced obesity and insulin resistance to model the effects of comorbid T2DM and obesity on vaccine immunogenicity and protection. Results
Mice fed a high-fat diet (HFD) developed obesity, hyperinsulinemia, and glucose intolerance. Relative to mice fed a normal diet (ND), HFD mice vaccinated with a SARS-CoV-2 mRNA vaccine exhibited significantly lower anti-spike IgG titers, predominantly in the IgG2c subclass, associated with a lower type 1 response, along with a 3.83-fold decrease in neutralizing titers. Furthermore, enhanced vaccine-induced spike-specific CD8+ T cell activation and protection from lung infection against SARS-CoV-2 challenge were seen only in ND mice but not in HFD mice. Conclusion
We demonstrate impaired immunity following SARS-CoV-2 mRNA immunization in a murine model of comorbid T2DM and obesity, supporting the need for further research into the basis for impaired anti-SARS-CoV-2 immunity in T2DM and investigation of novel approaches to enhance vaccine immunogenicity among those with metabolic diseases.
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