Immunoneutralisation of GnRH-I, without cross-reactivity to GnRH-II, in the development of a highly specific anti-fertility vaccine for clinical and veterinary use.
In recent years, several forms of gonadotrophin releasing hormone (GnRH) molecules have been isolated from primate brain. These molecules are very similar in sequence and this raises the question of whether previously developed neutralisation vaccines based on GnRH (now termed GnRH-I) would remove other forms of GnRH (namely GnRH-II) as well. As the function of these other molecules has not yet been clearly defined, potential health risks could exist by their ablation. In view of the high sequence homology between the molecules, this paper describes the production of highly specific polyclonal antibodies against GnRH-I and GnRH-II, with negligible cross-reactivity. The ultimate aim of this is to develop an anti-fertility vaccine which does not present any inappropriate side-effects, caused by neutralisation of a GnRH molecule which may or may not be directly involved in reproduction. Several formulations were investigated, based on analogues of the following molecules, conjugated to tetanus toxoid: 1. GnRH-I pGlu-His-Trp-Ser-Try-Gly-Leu-Arg-Pro-Gly-NH2 and 2. GnRH-II pGlu-His-Trp-Ser-His-Gly-Trp-Tyr-Pro-Gly-NH2. The specificity of the antibodies produced was examined, together with effects on fertility and any inappropriate side-effects. Immunostaining of hypothalamic sections was carried out, using the generated antisera, to determine the regional distribution of GnRH-I and GnRH-II neurones, as well as to further evaluate the specificity of the antibodies.
Ferro
V A
VA
Department of Immunology, University of Strathclyde, SIBS Building, 27 Taylor Street, Glasgow G4 ONR, UK. v.a.ferro@strath.ac.uk
Khan
M A
MA
Latimer
V S
VS
Brown
D
D
Urbanski
H F
HF
Stimson
W H
WH
D000818:Animals; D000918:Antibody Specificity; D001923:Brain Chemistry; D003272:Contraceptive Agents, Male / Q000009:adverse effects; D003429:Cross Reactions / Q000276:immunology; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007115:Immunization Schedule; D007132:Immunoglobulin Isotypes / Q000097:blood; D008253:Macaca mulatta; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013737:Testis / Q000033:anatomy & histology / Q000473:pathology; D013745:Tetanus Toxoid / Q000009:adverse effects / Q000276:immunology; D018074:Vaccines, Conjugate / Q000009:adverse effects / Q000276:immunology; D022642:Vaccines, Contraceptive / Q000009:adverse effects / Q000276:immunology*
D003272:Contraceptive Agents, Male; D007132:Immunoglobulin Isotypes; D013745:Tetanus Toxoid; D018074:Vaccines, Conjugate; D022642:Vaccines, Contraceptive; D007987:Gonadotropin-Releasing Hormone