Original article

Mic1-3 Knockout Toxoplasma gondii is a good candidate for a vaccine against T. gondii-induced abortion in sheep

¹ Université François Rabelais, INRA, UMR 0483 Université-INRA d’Immunologie Parasitaire, Vaccinologie et Biothérapie Anti-infectieuse, IFR136 Agents Transmissibles et Infectiologie, UFR de Pharmacie, 31 avenue Monge, 37200 Tours, France
² INRA, UR1282, Infectiologie Animale et Santé Publique, 37380 Nouzilly, France
³ VitamFero, UFR de Pharmacie, 31, avenue Monge, 37200 Tours, France
⁴ Université de Montpellier 2, CNRS, UMR 5539 Université-CNRS, 34090 Montpellier, France

^* Corresponding author: mevelec@univ-tours.fr

Received: 18 November 2009
Accepted: 12 April 2010

Abstract

This study assessed the effectiveness of a mutant strain of Toxoplasma gondii (RH strain) lacking the mic1 and mic3 genes (Mic1-3KO) against Toxoplasma abortion in sheep. Ewes were inoculated subcutaneously with 10⁵ Mic1-3KO tachyzoïtes in three independent experiments. Following vaccination, Mic1-3KO induced a mild febrile response and serum IgG antibodies, which persisted throughout the experiments. Tissue cysts formed in the sheep, but were not, under our experimental conditions, infectious when given orally. Ewes were mated two months after vaccination and were orally challenged with the PRU strain of T. gondii at mid-gestation (400 oocysts in Experiments 1 and 2; 100 oocysts in Experiment 3). Challenge of vaccinated pregnant ewes resulted in a slight febrile response, whereas unvaccinated ewes developed a more severe, characteristic febrile response of longer duration. After challenge, all unvaccinated ewes aborted whereas 62%, 91% and 64% (Experiments 1, 2 and 3 respectively) of the lambs from vaccinated ewes were viable, with no clinical signs of infection. Mic1-3KO was as effective as S48, the strain used as a live vaccine for sheep (Toxovax^®). A dose of 10⁵ Mic1-3KO tachyzoites was sufficient to induce protection (versus a dose of 2 × 10⁶). Both subcutaneous and intraperitoneal injections were effective. Moreover, preliminary results showed the potential of Mic1-3KO to reduce the development of tissue cysts in lambs born to vaccinated ewes. This study demonstrates that Mic1-3KO is a potent vaccine candidate.