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
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.