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

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).