Nasal immunization with different forms of heat shock protein-65 reduced high-cholesterol-diet-driven rabbit atherosclerosis

Heat shock protein-65 (Hsp65) is an important pro-atherogenic factor, but nasal immunization of Hsp65 can induce immune tolerance and reduce atherosclerotic inflammation. Here, we describe the effects of different forms of Hsp65 antigen inoculated, i.e. Hsp65 DNA, Hsp65 protein, Hsp65 DNA prime combined with Hsp65 protein boost, on high-cholesterol-diet-driven rabbit atherosclerosis lesions. The results showed that sera anti-Hsp65 IgG antibodies were lower induced and protective anti-Hsp65 IgA in nasal cavity and lung were induced after rabbits were immunized with different forms of Hsp65. However, the avidity between Hsp65 IgG antibody and antigen is different. Hsp65 DNA prime-protein boost could further improve the avidity compared with Hsp65 DNA immunization alone, but only immunization with Hsp65 protein alone obtain the best avidity. In addition, more protective IL-10 and less adverse IFN-γ were produced and sera TC and LDL-C were decreased obviously at different extents in immunized groups. As a result, atherosclerosis lesions were significantly attenuated, but only nasal immunization with Hsp65 protein alone may be the best effective form of Hsp65 antigen to control atherosclerotic lesions. The results demonstrated that different forms of Hsp65 antigen could produce different effects in the treatment of atherosclerosis. Immunization mucosally with Hsp65 protein could be a promising therapeutic method for atherosclerosis.

Highlights► Different forms of Hsp65 were immunized to rabbit with different patterns. ► The immunization effects of vaccine on rabbit atherosclerosis were evaluated. ► Sera antibody, avidity and cytokines were changed at a different degree. ► Sera lipids and atherosclerosis lesions were changed at a different degree. ► Immunization nasally with Hsp65 protein was a most promising choice.