Effects of nasal immunization of multi-target preventive vaccines on atherosclerosis.

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.