Parenteral administration of GnRH constructs and adjuvants: Immuneresponses and effects on reproductive tissues of male mice

Authors

Sameer Sharma, University of Canberra
Ian McDonald, University of Canberra
Lowell Martin, University of Canberra
Lyn A. Hinds, National Wildlife Research CenterFollow

Date of this Version

2014

Citation

Vaccine 32 (2014) 5555–5563.

Comments

U.S. government work.

Abstract

Two gonadotrophin releasing hormone (GnRH) constructs prepared by either chemical conjugation tokeyhole limpet hemocyanin (GnRH-KLH) or as an expressed recombinant fusion protein (Multimer) wereevaluated with or without adjuvants (immunostimulating complexes, ISCOMs, or cytosine-phosphate-guanosine oligodeoxynucleotides, CpG ODNs). After subcutaneous administration to Balb/c male mice atWeeks 0, 2 and 4, these preparations were assessed for induction of immune responses and effects onreproductive organs. GnRH-KLH plus ISCOMs formulation induced strong IgG immune responses fromWeek 4 through Week 12 resulting in consistent reproductive organ atrophy by Week 12 after sub-cutaneous administration. GnRH-KLH plus CpG ODNs generated immune responses but no atrophy ofreproductive tissues by Week 12. Multimer plus ISCOMs induced poor immune responses and no effectson reproductive tissues by Week 12. In the absence of additional adjuvant, none of the GnRH constructsinduced reproductive organ atrophy. GnRH-KLH induced stronger immune responses when formulatedwith ISCOMs or CpG ODN compared to Multimer. GnRH-KLH with ISCOMs could be an effective colloidalalternative for emulsion GnRH vaccine formulations.