Reversible contraception in female baboons immunized with a synthetic epitope of sperm-specific lactate dehydrogenase.
In previous experiments, the sperm-specific isozyme of lactate dehydrogenase (LDH-C) had been purified from mouse testes and shown to suppress the fertility of female baboons by 70% compared to controls. Although these results demonstrated the feasibility of this approach for contraceptive vaccine development, it is not practical to purify enough of the protein from natural sources for human use. Therefore, a need exists to develop a contraceptive vaccine based on synthetic peptides. In the current study, baboon LDH-C cDNA was amplified by the reverse transcriptase-polymerase chain reaction technique. The amino acid sequences of human and baboon LDH-C were 99.3% identical, indicating that the human LDH-C would be an effective antigen in nonhuman primates. The immunodominant epitope of human LDH-C was identified, synthesized, and conjugated to diphtheria toxoid (DT). This construct was used to immunize 15 female baboons; 15 control animals were immunized with DT alone. The fertility of the experimental group was reduced by 75% as compared to the controls (p < 0.02). One year after the last immunization, the contraceptive effect was completely eliminated (no statistical difference between the groups). These results show that a synthetic peptide based on the sequence of human LDH-C is effective in preventing pregnancy in nonhuman primates. The effect is completely reversed 1 yr after the last immunization. The contraceptive effect is not related to serum antibody titers, and human LDH-C is only slightly more effective than mouse LDH-C in female baboons.
O'Hern
P A
PA
Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois 60208-3500, USA.
Bambra
C S
CS
Isahakia
M
M
Goldberg
E
E
D000276:Adjuvants, Immunologic; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003269:Contraception, Immunologic; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D004168:Diphtheria Toxoid / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000276:immunology*; D007770:L-Lactate Dehydrogenase / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D008297:Male; D008969:Molecular Sequence Data; D010215:Papio; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology; D016133:Polymerase Chain Reaction; D013094:Spermatozoa / Q000201:enzymology*; D014614:Vaccines, Synthetic
D000276:Adjuvants, Immunologic; D018076:DNA, Complementary; D004168:Diphtheria Toxoid; D000939:Epitopes; D007527:Isoenzymes; D010446:Peptide Fragments; D014614:Vaccines, Synthetic; D007770:L-Lactate Dehydrogenase