Colinear synthesis of an antigen-specific B-cell epitope with a 'promiscuous' tetanus toxin T-cell epitope: a synthetic peptide immunocontraceptive.
Carrier conjugation is commonly used to provide T-cell help for small, linear peptides containing antigen-specific B-cell epitopes. However, carrier conjugation is expensive, variable and often results in adverse side effects if the conjugate is administered repeatedly. To eliminate the need for carrier conjugation, we examined two synthetic peptides for their ability to elicit sustained antibody titres in female rabbits and baboons. One peptide (hC1-20) was based on the sequence of the sperm-specific isozyme of human lactate dehydrogenase (LDH-C4). This peptide stimulates helper T-cell responses. The other peptide (bC5-19:TT) was a chimera between an LDH-C4 B-cell epitope and a 'promiscuous' T-cell epitope from tetanus toxin which has been shown to bind to and stimulate many different major histocompatibility complex alleles. Both peptides were immunogenic in rabbits and baboons. The chimera elicited consistently high antibody titres and was immunogenic in 19/19 wild-caught female baboons. When 14 bC5-19:TT immunized baboons were mated, their fertility was reduced by 62% compared with controls (P < 0.02). This carrier-free construct can be incorporated into biodegradable microspheres which may provide long-term protection from pregnancy with a single dose.
O'Hern
P A
PA
Center for Recombinant Gamete Vaccinogens, Northwestern University, Evanston, IL 60208, USA.
Liang
Z G
ZG
Bambra
C S
CS
Goldberg
E
E
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D003269:Contraception, Immunologic; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006239:Haplotypes; D007770:L-Lactate Dehydrogenase / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000276:immunology; D008297:Male; D008969:Molecular Sequence Data; D010215:Papio; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000138:chemical synthesis / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013744:Tetanus Toxin / Q000138:chemical synthesis* / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000737:chemistry* / Q000276:immunology*
D000939:Epitopes; D011993:Recombinant Fusion Proteins; D013744:Tetanus Toxin; D014614:Vaccines, Synthetic; D007770:L-Lactate Dehydrogenase