John Garner

PLGA-PEG-PLGA thermogel used in design of vaccine adjuvant as part of development of male contraceptive

Blog Post created by John Garner on Oct 8, 2019

In vaccines, an adjuvant is another substance or compound included to boost the immune response against the antigen. Thermogelling PLGA-PEG-PLGA can be used for this as it provides for extended release of the antigen as well as a slight pro-inflammatory response. Recently, there has been a great deal of research in the development of a male contraceptive that can be provided as a dosed medication (rather than a simple physical barrier such as a condom). This research has yielded Gonadotropin-releasing hormone as a target which can be blocked and subsequently prevent the downstream development of sperm.  Recently, researchers at Auburn University and Charles River Laboratories used PLGA-PEG-PLGA (AK097) from PolySciTech (www.polyscitech.com) to create a thermogel injection for male contraceptive and tested this in cats. This research holds promise to provide for improved reproductive control. Read more: Johnson, Aime K., Rebecca L. Jones, Carol J. Kraneburg, Anna M. Cochran, Alexandre M. Samoylov, James C. Wright, Cynthia Hutchinson et al. "Phage constructs targeting gonadotropin-releasing hormone for fertility control: evaluation in cats." Journal of Feline Medicine and Surgery (2019): 1098612X19875831. https://journals.sagepub.com/doi/abs/10.1177/1098612X19875831

 

“Abstract: Objectives: Phage–gonadotropin-releasing hormone (GnRH) constructs with potential contraceptive properties were generated in our previous study via selection from a phage display library using neutralizing GnRH antibodies as selection targets. In mice, these constructs invoked the production of antibodies against GnRH and suppressed serum testosterone. The goal of this study was to evaluate this vaccine against GnRH for its potential to suppress reproductive characteristics in cats. Methods: Sexually mature male cats were injected with a phage–GnRH vaccine using the following treatment groups: (1) single phage–GnRH vaccine with adjuvant; (2) phage–GnRH vaccine without adjuvant and half-dose booster 1 month later; or (3) phage–GnRH vaccine with adjuvant and two half-dose boosters with adjuvant 3 and 6 months later. Anti-GnRH antibodies and serum testosterone, testicular volume and sperm characteristics were evaluated monthly for 7–9 months. Results: All cats developed anti-GnRH antibodies following immunization. Serum antibody titers increased significantly after booster immunizations. In group 3, serum testosterone was suppressed 8 months after primary immunization. Total testicular volume decreased in group 1 by 24–42% and in group 3 by 15–36% at 7 months after immunization, indicating potential gonadal atrophy. Vacuolation of epididymides was observed histologically. Although all cats produced sperm at the conclusion of the study, normal morphology was decreased as much as 38%. Phage alone produced no local or systemic reactions. Immunization of phage with AdjuVac produced unacceptable injection site reactions. Conclusions and relevance: Our phage-based vaccine against GnRH demonstrated a potential for fertility impairment in cats. Future research is required to optimize vaccine regimens and identify animal age groups most responsive to the vaccine. If permanent contraception (highly desirable in feral and shelter cats) cannot be achieved, the vaccine has a potential use in zoo animals or pets where multiple administrations are more practical and/or reversible infertility is desirable. Keywords Fertility control, filamentous phage, gonadotropin-releasing hormone, GnRH”

Outcomes