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. 2013 Dec 27;8(12):e82765.
doi: 10.1371/journal.pone.0082765. eCollection 2013.

Intranasal immunisation with recombinant Toxoplasma gondii actin partly protects mice against toxoplasmosis

Li-Tian Yin  1 , Hai-Xia Hao  2 , Hai-Long Wang  3 , Jian-Hong Zhang  3 , Xiao-Li Meng  3 , Guo-Rong Yin  3
Affiliations

Intranasal immunisation with recombinant Toxoplasma gondii actin partly protects mice against toxoplasmosis

Li-Tian Yin et al. PLoS One. .

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Nasal immunisation induces rTgACT-specific IgG responses in sera.
Titres of both specific total IgG and IgG isotype antibodies in the sera of BALB/c mice were determined by ELISA with rTgACT as the bound target two weeks after the last immunisation. (A) Specific total IgG and (B) IgG1 and IgG2a titres in the sera of mice vaccinated with rTgACT. The results are expressed as the means of the OD492 ± SD (n = 10) and are representative of three experiments. *P<0.05, ** P<0.01 (vaccinated vs. PBS group).
Figure 2
Figure 2. Nasal immunisation induces rTgACT-specific SIgA responses in mucosal washes.
The SIgA antibody titres in mucosal washes from the mice were tested by ELISA two weeks after the last immunisation. High-level SIgA in (A) nasal washes, (B) vaginal washes and (C) intestinal washes were induced in mice nasally immunised with rTgACT compared to those vaccinated with PBS. **: Compared to PBS group, P<0.01. There were 6 mice per group, and the values are expressed as the mean ± SD. Significant differences were seen at P<0.01 (**) compared to mice immunised with PBS.
Figure 3
Figure 3. Assay for protection against oral challenge.
Mice were nasally immunised with rTgACT or PBS. Two weeks after the last immunisation, mice were orally challenged with tachyzoites. (A) Mice from two groups (n = 8 PBS and 8 rTgACT) were orally infected with 1×104 tachyzoites of the T. gondii RH strain. Liver and brain tachyzoite burdens were evaluated one month after challenge. (B) Mouse survival rates of the two groups (n = 12 PBS and 12 rTgACT) were monitored daily after challenge with 4×104 tachyzoites of T. gondii RH strain until day 30 post-challenge. Differences in survival were significant (P<0.01). These results are representative of two independent experiments. Values are means ± SD. * P<0.05, ** P<0.01. PBS, phosphate buffered saline.
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Grants and funding

This work was supported by the National Natural Science Foundation of China (No. 81071374). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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