Ovarian function following immunocontraceptive vaccination of mares using native porcine and recombinant zona pellucida vaccines formulated with a non-Freund's adjuvant and anti-GnRH vaccines

Abstract

An important determinant in the selection of any contraceptive agent is the impact on ovarian function, both in the short and longer term. In this study, ovarian activity was monitored in mares immunised with one of the following vaccine formulations; native porcine zona pellucida (pZP), recombinant zona pellucida proteins ZP3 and ZP4 (reZP), pZP and reZP combined or a commercially available anti-GnRH vaccine. The ZP antigens were prepared in an adjuvant formulation consisting of 6% polymeric adjuvant (Montanide™ PetGel A, Seppic, France) and 500 μg polyinosinic-polycytidylic acid - TLR3-agonist (Poly(I:C) HMW VacciGrade™, Invivogen, USA). A vehicle-only control group was administered the adjuvant formulation without antigen. Ovarian activity was monitored using clinical observations (transrectal palpation and ultrasonography of the reproductive tract) in addition to blood sampling for serum progesterone and anti-Müllerian hormone (AMH) concentrations while employing a low sampling frequency. Treatments and measurements were initiated in December (southern hemisphere summer) and subsequent data collection was performed in January, February, March and May. Both reZP and anti-GnRH vaccination were associated with clinically evident ovarian suppression in the short term. Ovarian activity in mares administered a reZP or anti-GnRH vaccine was significantly different to adjuvant control and pZP treated mares. Serum AMH concentrations were different between pZP and anti-GnRH treated mares 3.5 months after the final vaccination. Serum AMH concentrations were significantly correlated with mare age, serum progesterone and ovarian volume.

Evaluation of Stress Accompanying Immunocontraceptive Vaccination in Donkeys

“…The vaccination with reZP, pZP, and the injection of Freund’s adjuvant did not change the physical parameters (pulse, respiratory and rectal temperature) of the donkeys in the present study. Likewise, no heart and respiratory rate elevations were seen in horses vaccinated with reZP and pZP [ 32 , 33 ]. These findings are consistent with post-vaccinal (e.g., attenuated Venezuelan equine encephalomyelitis and inactivated equine herpesvirus) clinical parameters in horses and donkeys [ 34 , 35 , 36 , 37 ].…”

“…Body wall thicknesses, measured ultrasonographically, at the injection sites increased in each treatment group, peaking at day 2 post-vaccination. Previous immunocontraception studies have monitored injection site reactions but have only done so subjectively by observation and/or palpation of the injection sites [ 32 , 41 ]. Multiple other papers document the lack of injection site swelling associated with the administration of various vaccines but were also measured subjectively by observation and palpation [ 34 , 37 ].…”

“…Multiple other papers document the lack of injection site swelling associated with the administration of various vaccines but were also measured subjectively by observation and palpation [ 34 , 37 ]. In one study investigating ovarian dynamics and injection site reactions associated with administration of ZP and GnRH vaccines in mares, a 3-point scale to assess injection site reactions was used based upon palpation of the site and behavior reaction [ 32 ]. In the present study, only mild increases in body wall thickness were observed in the 4 days post-vaccination.…”

Suppression of reproductive behaviour and gonadal function in female horses—An update

“…Changes in ovarian function are most probably related to a cell‐related immune response to ZP‐based vaccines (Joonè et al., 2019 ). Antibody titres were a significant predictor of ovarian inactivity (Nolan et al., 2018 ).…”

Efficacy and Safety of Native and Recombinant Zona Pellucida Immunocontraceptive Vaccines Formulated with Non-Freund’s Adjuvants in Donkeys

“…The precise mechanism of this novel effect has yet to be clearly defined. However, the resultant suppression of ovarian activity (ovarian shutdown) is accompanied by anoestrus in these species [21,36,37].…”