This article is original from Translational Medicine Network. Please indicate the source when reprinting
Author: Lily
Introduction : Globally, diabetes (diabetes mellitus, DM) and obese people are growing - for example, among American adults, the prevalence rates of obesity and diabetes are as high as 41.9% and 14.8% respectively. has long been shown to be associated with increased risk of morbidity and death caused by a variety of infectious diseases, especially in older people with diabetes. Likewise, as with other factors such as aging, male and basic comorbidities (such as cardiovascular disease and chronic kidney disease ), diabetes and obesity are also risk factors for severe or mortality of COVID-19. We urgently need to prevent severe infections (especially the incidence of COVID-19) in these vulnerable populations to reduce the burden of disease.
The currently approved vaccine (including the SARS-CoV-2 BNT162b2 mRNA vaccine) is not as effective in patients with diabetes or obesity. After the mRNA vaccine against SARS-CoV-2 was put into use, relevant clinical studies have found that patients with type 2 diabetes (T2DM) — especially those with poor blood sugar control — have significantly reduced their humoral and cellular responses after receiving the SARS-CoV-2 vaccine. Similarly, a decrease in vaccine immunogenicity was also observed in obese adults, especially men. In conclusion, these findings suggest that metabolic disease impairs vaccine response and increases the risk of severe COVID-19.
However, it is not clear that the exact effect of metabolic disease on humoral and cellular immune responses after vaccination with SARS-CoV-2 vaccine is not clear; therefore, it is necessary to evaluate the causes of impaired vaccine response in patients with metabolic diseases, and explore the specific aspects of immunity being affected in order to provide vaccine optimization solutions for obese and diabetes groups.
About this study
01
On December 7, a research team from Harvard Medical School and other institutions in the United States published the latest research results on the bioRxiv website. This study evaluated the impact of metabolic diseases on the immunogenicity of the COVID-19 vaccine through a mouse model; the study showed for the first time that insulin resistance and obesity induced by a high-fat diet (HFD) will impair the humoral and cellular immunogenicity of the SARS-CoV-2 mRNA vaccine.
https://www.biorxiv.org/content/10.1101/2022.12.07.519460v1.full
Specifically, the researchers evaluated the effects of type 2 diabetes (T2DM) and obesity on the immune response of mice vaccinated with BNT162b2 vaccine—including antibody function, T cell response, and ability to fight severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
First, C57BL/6J mice were fed a high-fat diet (HFD) to establish obesity, hyperinsulinemia , hyperglycemia and glucose intolerance models; at the same time, control mice were fed a normal diet (ND). After
, the researchers immunized these high-fat diet (HFD) or normal diet (ND) mice with two doses of BNT162b2 mRNA or protein subunit vaccine (alum adjuvant recombinant SARS-CoV-2 spike receptor binding domain [RBD]).
results found that the BNT162b2 vaccine induced a strong humoral response; while the protein subunit vaccine elicited a limited antibody response in ND-fed mice. In addition, HFD-fed BNT162b2-immunized mice had 2.2-fold reduction in anti-spike immunoglobulin G (IgG) than ND-fed mice.
Next, the researchers evaluated the neutralization efficacy of immune serum in the surrogate and live-virus neutralization tests. After vaccination with the BNT162b2 vaccine, HFD-fed mice showed significantly attenuated neutralization efficacy compared with ND-fed mice. In addition, they also evaluated the correlation between fasting insulin levels and antibody responses in HFD-fed mice and found that serum insulin levels were negatively correlated with anti-spike immunoglobulin G (IgG) titer .
researchers harvested mouse spleen cells and stimulated the spleen cells with overlapping spike RBD peptides.ND-fed mice vaccinated with BNT162b2 vaccine showed higher levels of T-cell expression of interferon (IFN)-γ, tumor necrosis factor (TNF), and interleukin (IL)-2 compared with ND mice injected with phosphate buffered saline (PBS).
, in HFD mice, BNT162b2 vaccination did not cause significant induction of the cytokine mentioned above in HFD mice compared with the administration of phosphate buffered saline (PBS). Furthermore, ND-fed mice showed at least two times higher median cytokine levels than HFD-fed mice. Finally, through nasal exposure, the researchers exposed immunized mice to mouse-adapted live SARS-CoV-2 (103 plaque-forming units)
Before infection, the researchers measured the weight of mice—HFD-fed mice were significantly heavier than ND-fed mice. The animals were euthanized two days after infection and their lungs were harvested. All lung specimens have evidence of mild inflammation. The researchers determined the expression of chemokine, cytokines and IFN-stimulating genes in the lungs.
ND and HFD-fed mice injected with PBS showed high inflammatory responses in several genes. It is worth noting that ND mice immunized with the BNT162b2 vaccine had lower gene expression than those administered by PBS. However, there was no significant difference between BNT162b2 and PBS-managed HFD mice. HFD and ND mice administered with
PBS showed high viral load in the lungs . Mice immunized with protein subunit vaccine were not protected from infection. Pneumovirus titers decreased significantly compared with mice administered by PBS. In contrast, HFD-fed mice receiving BNT162b2 or PBS did not significantly differ in pneumovirus titers.
HFD-fed mice immunized with BNT162b2 vaccine had 262 times the pulmonary virus titers than ND-fed mice—although the differences were not statistically significant. The researchers observed that neutralization titers were negatively correlated with pulmonary virus titers, and that IFN-induced proteins were negatively correlated with the expression level of tetratripeptide repeat 2 (Ifit2).
Research significance
02
Although there is no SARS-CoV-2 vaccine tailored for obesity or type 2 diabetes (T2DM) patients, strategies for developing precise vaccines for specific age groups have been studied. Consistent with this study of methods to simulate metabolic diseases, the age-specific mouse model showed reduced immunogenicity, increased mortality and morbidity, and decreased immunity in elderly mice, which was comparable to the observation results of the elderly. The booster of mRNA vaccine provides sterilized immunity to lung infections in for 21-month-old mice, while young mice are protected without booster, suggesting the importance of age-specific vaccine protocols. By developing appropriate adjuvants for SARS-CoV-2 protein-based vaccines, greater protective effects were observed in elderly mice despite the age-related decline in immunity.
is based on this precedent, and this study hypothesized that similar approaches could help overcome the deficiencies associated with metabolic disease in vaccine responses. It is worth noting that adjuvants can not only enhance vaccine immunity, but also shape the polarization of immune responses. Therefore, definition of the best adjuvant formulation may be a promising method to overcome the reduction of Th1 polarization observed in diabetic obese mice in this study.
Reference:
https://www.news-medical.net/news/20221213/Obesity-and-type-2-diabetes-impair-mRNA-COVID-vaccine-efficacy-in-mouse-model.aspx
https://www.biorxiv.org/content/10.1101/2022.12.07.519460v1.full
Note: This article aims to introduce the progress of medical research and cannot be used as a reference for treatment plans. If you need health guidance, please go to a regular hospital for treatment.
Click to participate in "My 2022"
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-