TY - JOUR
T1 - Parenteral administration of GnRH constructs and adjuvants
T2 - Immune responses and effects on reproductive tissues of male mice
AU - Sharma, Sameer
AU - McDonald, Ian
AU - Miller, Lowell
AU - HINDS, Lyn
PY - 2014/9/29
Y1 - 2014/9/29
N2 - Two gonadotrophin releasing hormone (GnRH) constructs prepared by either chemical conjugation to keyhole limpet hemocyanin (GnRH-KLH) or as an expressed recombinant fusion protein (Multimer) were evaluated with or without adjuvants (immunostimulating complexes, ISCOMs, or cytosine-phosphate-guanosine oligodeoxynucleotides, CpG ODNs). After subcutaneous administration to Balb/c male mice at Weeks 0, 2 and 4, these preparations were assessed for induction of immune responses and effects on reproductive organs. GnRH-KLH plus ISCOMs formulation induced strong IgG immune responses from Week 4 through Week 12 resulting in consistent reproductive organ atrophy by Week 12 after subcutaneous administration. GnRH-KLH plus CpG ODNs generated immune responses but no atrophy of reproductive tissues by Week 12. Multimer plus ISCOMs induced poor immune responses and no effects on reproductive tissues by Week 12. In the absence of additional adjuvant, none of the GnRH constructs induced reproductive organ atrophy. GnRH-KLH induced stronger immune responses when formulated with ISCOMs or CpG ODN compared to Multimer. GnRH-KLH with ISCOMs could be an effective colloidal alternative for emulsion GnRH vaccine formulations.
AB - Two gonadotrophin releasing hormone (GnRH) constructs prepared by either chemical conjugation to keyhole limpet hemocyanin (GnRH-KLH) or as an expressed recombinant fusion protein (Multimer) were evaluated with or without adjuvants (immunostimulating complexes, ISCOMs, or cytosine-phosphate-guanosine oligodeoxynucleotides, CpG ODNs). After subcutaneous administration to Balb/c male mice at Weeks 0, 2 and 4, these preparations were assessed for induction of immune responses and effects on reproductive organs. GnRH-KLH plus ISCOMs formulation induced strong IgG immune responses from Week 4 through Week 12 resulting in consistent reproductive organ atrophy by Week 12 after subcutaneous administration. GnRH-KLH plus CpG ODNs generated immune responses but no atrophy of reproductive tissues by Week 12. Multimer plus ISCOMs induced poor immune responses and no effects on reproductive tissues by Week 12. In the absence of additional adjuvant, none of the GnRH constructs induced reproductive organ atrophy. GnRH-KLH induced stronger immune responses when formulated with ISCOMs or CpG ODN compared to Multimer. GnRH-KLH with ISCOMs could be an effective colloidal alternative for emulsion GnRH vaccine formulations.
KW - Cytosine-phosphate-guanosine oligodeoxynucleotides
KW - Endogenous peptide
KW - Epididymis
KW - Immunostimulating complexes
KW - Testis
KW - Vaccine
UR - http://www.scopus.com/inward/record.url?scp=84908406945&partnerID=8YFLogxK
UR - http://www.mendeley.com/research/parenteral-administration-gnrh-constructs-adjuvants-immune-responses-effects-reproductive-tissues-ma
U2 - 10.1016/j.vaccine.2014.07.075
DO - 10.1016/j.vaccine.2014.07.075
M3 - Article
SN - 0264-410X
VL - 32
SP - 5555
EP - 5563
JO - Vaccine
JF - Vaccine
IS - 43
ER -