Intranasal immunization with chitosan/pCETP nanoparticles inhibits atherosclerosis in a rabbit model of atherosclerosis.
In search of a convenient and pain-free route of administration of DNA vaccine against atherosclerosis, the plasmid pCR-X8-HBc-CETP (pCETP) encoding B-cell epitope of cholesteryl ester transfer protein C-terminal fragment displayed by Hepatitis B virus core particle was condensed with chitosan to form chitosan/pCETP nanoparticles. Cholesterol-fed rabbits were then intranasally immunized with the chitosan/pCETP nanoparticles to evaluate antiatherogenic effects. The results showed that significant serum antibodies against CETP were detected by enzyme-linked immunosorbent analysis and verified by Western blot analysis. The significant anti-CETP IgG lasted for 21 weeks in the rabbits immunized intranasally. Moreover, the atherogenic index was significantly lower compared with the saline control (5.95 versus 2.39, p<0.05). In addition, the average percentage of aortic lesions in the entire aorta area in the rabbits intranasally vaccinated with nanoparticles was 59.2% less than those treated with saline (29.0+/-10.9% versus 71.0+/-14.4%, p<0.01) and was similar to those intramuscularly injected with pCETP solution (29.0+/-10.9% versus 21.2+/-14.2%, p>0.05). Thus, chitosan/pCETP nanoparticles could significantly attenuate the progression of atherosclerosis by intranasal immunization. The results suggested that intranasal administration could be potentially developed as a vaccination route against atherosclerosis.
Institute of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Tong Jia Xiang 24, Nanjing 210009, Jiangsu, People's Republic of China.
Xiying
X
Yuan
Xiaorong
X
Yang
Danning
D
Cai
Dan
D
Mao
Jie
J
Wu
Li
L
Zong
Jingjing
J
Liu
D000281:Administration, Intranasal; D000818:Animals; D000906:Antibodies / Q000097:blood; D001011:Aorta / Q000473:pathology; D050197:Atherosclerosis / Q000517:prevention & control*; D015153:Blotting, Western; D048271:Chitosan / Q000008:administration & dosage*; D053480:Cholesterol Ester Transfer Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006512:Hepatitis B Core Antigens / Q000235:genetics; D006515:Hepatitis B virus; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D007273:Injections, Intramuscular; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage*; D010957:Plasmids; D011817:Rabbits; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
D000906:Antibodies; D053480:Cholesterol Ester Transfer Proteins; D006512:Hepatitis B Core Antigens; D007074:Immunoglobulin G; D019444:Vaccines, DNA; D048271:Chitosan