Blocking of pregnancy in mice by immunization with anti-idiotype directed against monoclonal anti-progesterone antibody.
Passive transfer of monoclonal anti-progesterone antibodies shortly after mating blocks the onset of pregnancy in different species (mouse, rat, and ferret). Here we report that BALB/c mice can be actively immunized against progesterone, and hence against pregnancy, by means of rabbit anti-idiotypic antibodies specific for a mouse monoclonal anti-progesterone antibody, DB3. Some of the anti-idiotypic antibodies reacted with the steroid-combining site on the DB3 molecule. In response to repeated anti-idiotypic immunization, mice produced serum anti-progesterone antibodies (up to 100 micrograms/ml) that resembled DB3 in idiotypy, affinity, and specificity for progesterone and other steroid ligands. Thus an anti-idiotype can mimic the antigenicity of a steroid hormone with a high degree of accuracy. Compared with immunization with a progesterone-bovine serum albumin conjugate, the anti-progesterone response to anti-idiotype was considerably lower and clonally restricted. When mated after completion of the immunization course, the fertility rate of anti-idiotype-immunized mice was reduced to 30% from a control level of 91%. The anti-fertility effect was correlated with the circulating anti-progesterone concentration in individual animals and persisted for 4 or 5 estrous cycles. Active immunization with progesterone-bovine serum albumin was a highly effective means of rendering mice infertile; it reduced the fertility rate to zero over 16 or 17 estrous cycles. Our results suggest that anti-idiotypes may form the basis of contraceptive vaccines.
Department of Immunology, Institute of Animal Physiology and Genetics Research, Babraham, Cambridge, England.
M W
MW
Wang
R B
RB
Heap
M J
MJ
Taussig
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D003429:Cross Reactions; D005260:Female; D007116:Immunization, Passive; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000276:immunology*; D011374:Progesterone / Q000276:immunology* / Q000502:physiology
D000911:Antibodies, Monoclonal; D007130:Immunoglobulin Idiotypes; D011374:Progesterone