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Reversible contraception in female baboons immunized with a synthetic epitope of sperm-specific lactate dehydrogenase
Ist Teil von
Biology of reproduction, 1995-02, Vol.52 (2), p.331-339
Ort / Verlag
Madison, WI: Society for the Study of Reproduction
Erscheinungsjahr
1995
Quelle
Electronic Journals Library
Beschreibungen/Notizen
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.