REVERSIBLE CONTRACEPTION IN FEMALE BABOONS IMMUNIZED WITH A SYNTHETICEPITOPE OF SPERM-SPECIFIC LACTATE-DEHYDROGENASE

Citation
Pa. Ohern et al., REVERSIBLE CONTRACEPTION IN FEMALE BABOONS IMMUNIZED WITH A SYNTHETICEPITOPE OF SPERM-SPECIFIC LACTATE-DEHYDROGENASE, Biology of reproduction, 52(2), 1995, pp. 331-339
Citations number
49
Categorie Soggetti
Reproductive Biology
Journal title
ISSN journal
00063363
Volume
52
Issue
2
Year of publication
1995
Pages
331 - 339
Database
ISI
SICI code
0006-3363(1995)52:2<331:RCIFBI>2.0.ZU;2-Z
Abstract
In previous experiments, the sperm-specific isozyme of lactate dehydro genase (LDH-C) had been purified from mouse testes and shown to suppre ss the fertility of female baboons by 70% compared to controls. Althou gh these results demonstrated the feasibility of this approach for con traceptive vaccine development, it is not practical to purify enough o f the protein from natural sources for human use. Therefore, a need ex ists to develop a contraceptive vaccine based on synthetic peptides. I n the current study, baboon LDH-C cDNA was amplified by the reverse tr anscriptase-polymerase chain reaction technique. The amino acid sequen ces of human and baboon LDH-C were 99.3% identical, indicating that th e 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 toroid (DT). This construct was used to immu nize 15 female baboons; 15 control animals were immunized with DT alon e. The fertility of the experimental group was reduced by 75% as compa red to the controls (p < 0.02). One year after the last immunization, the contraceptive effect was completely eliminated (no statistical dif ference between the groups). These results show that a synthetic pepti de based on the sequence of human LDH-C is effective in preventing pre gnancy in nonhuman primates. The effect is completely reversed 1 yr af ter 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.