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Ecology, management and conservation in natural and modified habitats
RESEARCH ARTICLE

Controlled-release components of PZP contraceptive vaccine extend duration of infertility

John W. Turner Jr A F , Allen T. Rutberg B , Ricky E. Naugle B , Manpreet A. Kaur C , Douglas R. Flanagan C , Henk J. Bertschinger D and Irwin K. M. Liu E
+ Author Affiliations
- Author Affiliations

A Physiology and Pharmacology, University of Toledo College of Medicine, Toledo, OH 43614, USA.

B Department of Environmental and Population Health, Tufts–Cummings School of Veterinary Medicine, North Grafton, MA 01536, USA.

C University of Iowa, Iowa City, IA 52242, USA.

D Department of Theriogenology, Faculty of Veterinary Medicine, University of Pretoria, Onderstepoort 0110, South Africa.

E Department of Population Health and Reproduction, School of Veterinary Medicine, University of California–Davis, Davis, CA 95616, USA.

F Corresponding author. Email: john.turner@utoledo.edu

Wildlife Research 35(6) 555-562 https://doi.org/10.1071/WR07159
Submitted: 12 October 2007  Accepted: 2 May 2008   Published: 22 October 2008

Abstract

Successful immunocontraception of wildlife relying on repeated access to individuals for boosters has highlighted the need to incorporate primer and booster immunisations into one injection. We have investigated use of controlled-release polymers (lactide–glycolide) in small pellets to provide delayed in vivo delivery of booster porcine zona pellucida (PZP) antigen and adjuvant. This report reviews pellet-making methodology, in vitro testing of controlled-release pellets and in vivo effects of controlled-release PZP vaccine. We assessed 3 different manufacturing approaches for producing reliable, cost-effective pellets: (1) polymer melting and extrusion; (2) solvent evaporation from polymer solution; and (3) punch and die polymer moulding. In vitro testing of release patterns of controlled-release formulations, towards development of a 3-year duration vaccine, provided estimates for in vivo use of pellet preparations. These in vitro studies demonstrated protein release delay up to 22 months using 100% l-lactide or polycaprolactone polymers. For in vivo tests, pellets (1-, 3-, and 12-month release delay) serving as boosters were administered intramuscularly with PZP/adjuvant liquid primer to wild horses (Equus caballus), white-tailed deer (Odocoileus virginanus) and African elephants (Loxodonta africana). Horse field studies assessed fertility via offspring counts and/or faecal-hormone pregnancy testing. Treatment decreased fertility 5.3–9.3-fold in Year 1 and 3.6-fold in Year 2. In preliminary testing in deer, offspring counts revealed treatment-associated fertility reduction of 7.1-fold Year 1 and 3.3-fold Year 2. In elephants, treatment elevated anti-PZP titres 4.5–6.9-fold from pretreatment (no fertility data).


Acknowledgements

Thanks to: M. Kaur, E. Philbrick, T. Hogan, T. Kennedy and E. Schmidt for in vitro work and pellet preparation; M. Miller-Jasper for administrative and secretarial work; and R. VanRossum for elephant titre work. Thanks to our numerous assistants for field monitoring. These studies were supported by the USA Department of Interior Bureau of Land Management, the Humane Society of the United States and the University of Toledo College of Medicine.


References

Carter, D. H. , Luttinger, M. , and Gardner, D. L. (1988). Controlled release parenteral systems for veterinary applications. Journal of Controlled Release 8, 15–22.
Crossref | GoogleScholarGoogle Scholar | CAS | Linhardt R. J. (1989). Biodegradable polymers for the controlled polymers. In ‘Controlled Release of Drugs, Polymer and Aggregate Systems’. (Ed. M. Rosoff.) pp. 53–95. (VCH Publishers: New York.)

Liu, I. K. M. , Bernoco, M. , and Feldman, M. (1989). Contraception in mares heteroimmunized with porcine zona pellucida. Journal of Reproduction and Fertility 85, 19–29.
CAS | PubMed | Zar J. H. (1984). ‘Biostatistical Analysis.’ (Prentice-Hall: Englewood Cliffs, NJ.)