Enhanced immunogenicity of peptide P277 by heat shock protein HSP65 vector carrying tandem repeats of P277 to prevent type 1 diabetes in NOD mice.
The peptide P277 contains a target epitope for diabetogenic T cells and it has been used as an ideal target antigen to develop vaccines against type 1 diabetes. A major problem in developing P277 vaccine is its low immunogenicity. Recent applications involving multiple copies of self-peptide in linear alignment and conjugation with carrier proteins appear to increase the immune response. In this study, we designed a method based on isocaudamer technique to repeat tandemly the 24-residue sequence P277, then 6 tandemly repeated copies of the peptide P277 were fused to mycobacterial heat-shock protein 65 to construct a fusion protein HSP65-6xP277 as an immunogen. We examined the effect of the tandem repeats of the peptide P277 in eliciting an immune response by comparing the immunogenicity of the three immunogens: P277, HSP65-P277 and HSP65-6xP277. Immunization of mice with the fusion protein HSP65-6xP277 elicited much higher levels of specific anti-P277 antibodies than with P277 and HSP65-P277, which should suggest that multiple tandem repeats of a certain epitope is an efficient method to overcome the low immunogenicity of self-peptide antigens and the immunogen HSP65-6xP277 might be further developed to a vaccine against type 1 diabetes.
Liang
J
J
Minigene Pharmacy Laboratory, Biopharmaceutical College, China Pharmaceutical University, Nanjing, PR China.
Aihua
Z
Z
Yu
W
W
Jingjing
L
L
D000818:Animals; D000906:Antibodies / Q000276:immunology; D001500:BCG Vaccine / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D018834:Chaperonin 60; D018833:Chaperonins / Q000235:genetics / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000473:pathology; D000939:Epitopes / Q000276:immunology; D005260:Female; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D007118:Immunoassay; D051379:Mice; D016688:Mice, Inbred NOD; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology*; D014612:Vaccines
D000906:Antibodies; D001500:BCG Vaccine; D001426:Bacterial Proteins; D018834:Chaperonin 60; D000939:Epitopes; D006360:Heat-Shock Proteins; D010446:Peptide Fragments; D014612:Vaccines; C074119:heat-shock protein 65, Mycobacterium; C095402:peptide 277, heat shock protein 60; D018833:Chaperonins