Abstract
Toxoplasma gondii is a ubiquitous protozoan intracellular parasite, the causative agent of toxoplasmosis, and a worldwide zoonosis for which an effective vaccine is needed. Actin is a highly conserved microfilament protein that plays an important role in the invasion of host cells by T. gondii. This study investigated the immune responses elicited by BALB/c mice after nasal immunisation with a recombinant T. gondii actin (rTgACT) and the subsequent protection against chronic and lethal T. gondii infections. We evaluated the systemic response by proliferation, cytokine and antibody measurements, and we assessed the mucosal response by examining the levels of TgACT-specific secretory IgA (SIgA) in nasal, vaginal and intestinal washes. Parasite load was assessed in the liver and brain, and the survival of mice challenged with a virulent strain was determined. The results showed that the mice immunised with rTgACT developed high levels of specific anti-rTgACT IgG titres and a mixed IgG1/IgG2a response with a predominance of IgG2a. The systemic immune response was associated with increased production of Th1 (IFN-γ and IL-2), Th2 (IL-4) and Treg (IL-10) cytokines, indicating that not only Th1-type response was induced, but also Th2- and Treg-types responses were induced, and the splenocyte stimulation index (SI) was increased in the mice immunised with rTgACT. Nasal immunisation with rTgACT led to strong mucosal immune responses, as seen by the increased secretion of SIgA in nasal, vaginal and intestinal washes. The vaccinated mice displayed significant protection against lethal infection with the virulent RH strain (survival increased by 50%), while the mice chronically infected with RH exhibited lower liver and brain parasite loads (60.05% and 49.75%, respectively) than the controls. Our data demonstrate, for the first time, that actin triggers a strong systemic and mucosal response against T. gondii. Therefore, actin may be a promising vaccine candidate against toxoplasmosis.
Highlights
Toxoplasma gondii, the causative agent of toxoplasmosis, is a widespread opportunistic pathogen capable of invading virtually all nucleated cells of warm-blooded animals
To assess whether mice immunised with recombinant T. gondii actin (rTgACT) induced immune protection against T. gondii infection, we investigated the systemic and mucosal immune responses elicited by BALB/c mice after nasal immunisation with rTgACT and protection against chronic and lethal T. gondii infections
The results showed that 30 mg and 40 mg of rTgACT could elicit the maximum IgG antibody responses compared to the 10 mg and 20 mg rTgACT groups (P,0.05), but no significant differences were observed in the IgG responses between higher and lower dose groups (P.0.05)
Summary
Toxoplasma gondii, the causative agent of toxoplasmosis, is a widespread opportunistic pathogen capable of invading virtually all nucleated cells of warm-blooded animals. Toxoplasmosis is generally asymptomatic in healthy individuals, it may provoke severe problems in immunodeficient individuals, such as AIDS patients, whereby T. gondii infection can cause encephalitis, pneumonia and disseminated infections [3]. T. gondii infection in farm animals has considerable economic importance, as it causes abortion, stillbirth and neonatal loss, especially in sheep [6]. T. gondii control depends primarily on chemotherapy, but the available drugs have many side effects along with problems of reactivation. The poor results of the available treatment options have led to pleas for developing an effective vaccine [8]. The development of safe and effective vaccines is the best strategy for the prevention of toxoplasmosis [11,12]
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