TY - JOUR
T1 - Investigation into suitable carrier molecules for use in an anti-gonadotrophin releasing hormone vaccine
AU - Ferro, V. A.
AU - Stimson, W. H.
PY - 1998/7/31
Y1 - 1998/7/31
N2 - Gonadal function can be controlled through immunoneutralisation of gonadotrophin releasing hormone (GnRH), with an analogue, GnRH-glycys, linked to a carrier molecule and an appropriate adjuvant. In this study, four different types of carrier molecule were investigated: (a) single and branched amino acid polymers--[poly-(D-glu, D-lys) and poly-(phe, glu)-poly(DL-ala)-poly(lys)]; (b) bacterial toxoids--diphtheria (DT) and tetanus (TT); (c) synthetic T-helper epitopes--derived from malarial circumsporozite protein (CS) and measles virus fusion protein (MVF); and (d) thyroglobulin (Thy)--a large protein. The effect of non-ionic surfactant vesicles (NISV) and an aluminum hydroxide based adjuvant (alum), was also examined. Although good antibody responses were achieved with GnRH-glycys-DT, GnRH-glycys-TT and GnRH-glycys-Thy, adsorbed onto alum and the dimerised synthetic T-helper epitope constructs, incorporated into NISV, a critical antibody titre was necessary to result in morphological changes in the gonads and complete suppression of spermatogenesis. This was only achieved with tetanus toxoid and the dimerised T-helper epitopes.
AB - Gonadal function can be controlled through immunoneutralisation of gonadotrophin releasing hormone (GnRH), with an analogue, GnRH-glycys, linked to a carrier molecule and an appropriate adjuvant. In this study, four different types of carrier molecule were investigated: (a) single and branched amino acid polymers--[poly-(D-glu, D-lys) and poly-(phe, glu)-poly(DL-ala)-poly(lys)]; (b) bacterial toxoids--diphtheria (DT) and tetanus (TT); (c) synthetic T-helper epitopes--derived from malarial circumsporozite protein (CS) and measles virus fusion protein (MVF); and (d) thyroglobulin (Thy)--a large protein. The effect of non-ionic surfactant vesicles (NISV) and an aluminum hydroxide based adjuvant (alum), was also examined. Although good antibody responses were achieved with GnRH-glycys-DT, GnRH-glycys-TT and GnRH-glycys-Thy, adsorbed onto alum and the dimerised synthetic T-helper epitope constructs, incorporated into NISV, a critical antibody titre was necessary to result in morphological changes in the gonads and complete suppression of spermatogenesis. This was only achieved with tetanus toxoid and the dimerised T-helper epitopes.
KW - immunogenicity
KW - carrier molecules
KW - GnRH analogue
KW - gonadal function
UR - http://www.sciencedirect.com/science/journal/0264410X
U2 - 10.1016/S0264-410X(98)80104-7
DO - 10.1016/S0264-410X(98)80104-7
M3 - Article
C2 - 9682364
SN - 0264-410X
VL - 16
SP - 1095
EP - 1102
JO - Vaccine
JF - Vaccine
IS - 11-12
ER -