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Published on: September 22, 2023
Effects of nasal immunization of multi-target preventive vaccines on atherosclerosis
Long Jun1, Lin Jie, Yuan Dongping
1Department of Clinic Pharmacy, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China.
Abstract:
Previous investigations have demonstrated that anti-inflammatory or lipid-lowering treatments could be useful for alleviating morbidity and mortality of atherosclerotic cardiovascular diseases. However, whether a vaccine designed to target inflammation and lipid simultaneously is more powerful to control the process of atherosclerosis remain to be unknown. Here, a vaccine was designed to target heat shock protein-65(Hsp65) and cholesteryl ester transfer protein (CETP) simultaneously and the effects of nasal immunization of multi-target vaccine on high-cholesterol-diet-driven rabbit atherosclerosis lesions were evaluated. Sera, nasal lavages and lung washes were used to ELISA assay for the analysis of IgG and IgA against Hsp65 and CETP. Sera were also used to the analysis of the avidity of combination of anti-Hsp65 and anti-CETP IgG antibodies with corresponding antigen, cytokines IL-10 and IFN-γ, and lipoproteins. In addition, aortas were harvested for analysis of atherosclerotic lesions. The results showed that lower and lasting specific anti-Hsp65 IgG and high anti-CETP IgG in sera and protective anti-Hsp65 and anti-CETP IgA in nasal cavity and lung were induced, the avidity of combination of anti-Hsp65 and anti-CETP IgG with antigen were higher, and more protective IL-10 and less adverse IFN-γ were produced. In addition, sera TC, and LDL-C were decreased. As a result, the size of aorta atherosclerotic plaques was significantly reduced. We conclude that multifaceted vaccine combining lipid-regulating with anti-inflammation was a potential remedy, especially for atherosclerosis with complicated etiology.
Insights
A novel vaccine targeting both heat shock protein-65 (Hsp65) and cholesteryl ester transfer protein (CETP) reduced atherosclerosis in rabbits. This dual-action vaccine shows promise for treating complex cardiovascular diseases.
Area of Science:
- Immunology
- Cardiovascular Science
- Vaccinology
Background:
- Atherosclerotic cardiovascular diseases involve inflammation and lipid dysregulation.
- Existing anti-inflammatory or lipid-lowering treatments offer partial benefits.
- The efficacy of a combined anti-inflammatory and lipid-targeting vaccine for atherosclerosis is unknown.
Purpose of the Study:
- To develop and evaluate a multi-target vaccine against heat shock protein-65 (Hsp65) and cholesteryl ester transfer protein (CETP).
- To assess the vaccine's impact on high-cholesterol-diet-induced rabbit atherosclerosis lesions via nasal immunization.
Main Methods:
- Nasal immunization with a dual-target vaccine (anti-Hsp65 and anti-CETP).
- ELISA assays for IgG and IgA in sera, nasal lavages, and lung washes.
- Analysis of antibody avidity, cytokine profiles (IL-10, IFN-γ), and lipoproteins.
- Histopathological assessment of aortic atherosclerotic lesions.
Main Results:
- Induction of lasting anti-Hsp65 IgG and high anti-CETP IgG in sera.
- Generation of protective anti-Hsp65 and anti-CETP IgA in mucosal sites (nasal cavity, lungs).
- Increased antibody avidity, elevated IL-10, reduced IFN-γ, and decreased serum total cholesterol (TC) and LDL-C.
- Significant reduction in the size of aortic atherosclerotic plaques.
Conclusions:
- A multifaceted vaccine targeting both inflammation (Hsp65) and lipid metabolism (CETP) is effective in reducing atherosclerosis.
- Nasal immunization with this dual-action vaccine offers a potential therapeutic strategy for atherosclerosis.
- This approach may be particularly beneficial for atherosclerosis with complex underlying causes.
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