Abstract 1490: Vaccination for Atherosclerosis in apo E (−/−) Mice: Comparative Efficacy of Native Versus MDA-modified Apo B-100 Related Peptide Antigen and Subcutaneous Versus Intranasal Immunization
Background We have previously shown that immunization with certain apoB-100 related peptide antigens reduce atherosclerosis. In this study, we compared the athero-protective efficacy of immunization using native or MDA modified antigen delivered subcutaneously or intranasally.
Methods and results: For subcutaneous immunization, apo E (−/−) mice were immunized at 6, 9 and 11 weeks of age with native or MDA-modified peptides P210 (amino acids 3136 ′3155, KTTKQ SFDLS VKAQY KKNKH) or P45 (amino acids 688–707, IEIGL EGKGF EPTLE ALFGK) conjugated with cBSA with alum as adjuvant. For intranasal immunization, mice were immunized with peptide 210 with CTB as adjuvant twice weekly at 6, 7, 8, 9, 10 weeks of age. High cholesterol diet was started at 12 weeks of age until sacrifice at 25 weeks. En face aortic preparation was assessed for the extent of atherosclerosis. Subcutaneous immunization with native P210 resulted in a 50% (p=0.001) reduction in aortic atherosclerosis when compared to cBSA/Alum control group; whereas P45 was less effective. Immunization with MDA modified peptide did not confer atheroprotection when compared to native form. Anti-p210 IgM titers were increased in p210 or p45 immunized mice, indicating possible cross-reactivity; whereas anti-p45 IgM increased only in p45 immunized mice. There was no increase in IgG titer (Table⇓). Intranasal immunization with P210 did not confer atheroprotection (P210-CTB 5.5±3.3%, n=13; CTB 6.1±2.6%, n=14). Immunization did not affect circulating cholesterol levels and body weight.
Conclusion: Our data suggest that:
immunization with native apoB-100 peptide antigen (P210) is more athero-protective than the use of MDA modified P210 and
Subcutaneous immunization is more effective than intranasal delivery of the antigen.