Abstract
Toxoplasmosis, a zoonotic disease caused by Toxoplasma gondii, is an important public health problem and veterinary concern. Although there is no vaccine for human toxoplasmosis, many attempts have been made to develop one. Promising vaccine candidates utilize proteins, or their genes, from microneme organelle of T. gondii that are involved in the initial stages of host cell invasion by the parasite. In the present study, we used different recombinant microneme proteins (TgMIC1, TgMIC4, or TgMIC6) or combinations of these proteins (TgMIC1-4 and TgMIC1-4-6) to evaluate the immune response and protection against experimental toxoplasmosis in C57BL/6 mice. Vaccination with recombinant TgMIC1, TgMIC4, or TgMIC6 alone conferred partial protection, as demonstrated by reduced brain cyst burden and mortality rates after challenge. Immunization with TgMIC1-4 or TgMIC1-4-6 vaccines provided the most effective protection, since 70% and 80% of mice, respectively, survived to the acute phase of infection. In addition, these vaccinated mice, in comparison to non-vaccinated ones, showed reduced parasite burden by 59% and 68%, respectively. The protective effect was related to the cellular and humoral immune responses induced by vaccination and included the release of Th1 cytokines IFN-γ and IL-12, antigen-stimulated spleen cell proliferation, and production of antigen-specific serum antibodies. Our results demonstrate that microneme proteins are potential vaccines against T. gondii, since their inoculation prevents or decreases the deleterious effects of the infection.
Highlights
T. gondii is an obligate intracellular protozoan parasite that infects warm-blooded animals and causes toxoplasmosis
We have previously reported that a lactose-affinity fraction (Lac+) purified from the soluble tachyzoite antigen of the T. gondii RH strain is constituted of T. gondii microneme protein 1 (TgMIC1) and TgMIC4, and that vaccination of C57BL/6 mice with Lac+ induces protective immunity against T. gondii [20, 21]
The immunoreactivity of TgMIC1 and TgMIC4 preparations with anti-Lac+ mouse serum was confirmed by western blot analysis; no reactivity was observed with TgMIC6 preparation (Fig 1, panel E)
Summary
T. gondii is an obligate intracellular protozoan parasite that infects warm-blooded animals and causes toxoplasmosis. This wide host range makes T. gondii one of the most successful protozoan parasites. Toxoplasmosis can cause substantial economic losses to the farming industry [8, 9]. The development of an effective vaccine or immunotherapy against human toxoplasmosis would be valuable for preventing both primary fetal infection and reactivation in immunocompromised individuals. Vaccination might reduce economic losses by preventing abortions in farm animals. The characterization of molecules that play a role in the pathogenesis of T. gondii infection may constitute an important step in vaccine development
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