RHΔ<i>gra17</i>Δ<i>npt1</i> Strain of <i>Toxoplasma gondii</i> Elicits Protective Immunity Against Acute, Chronic and Congenital Toxoplasmosis in Mice

oleh: Qin-Li Liang, Li-Xiu Sun, Hany M. Elsheikha, Xue-Zhen Cao, Lan-Bi Nie, Ting-Ting Li, Tao-Shan Li, Xing-Quan Zhu, Jin-Lei Wang

Format: Article
Diterbitkan: MDPI AG 2020-03-01

Deskripsi

<b>: </b>In the present study, a dense granule protein 17 (<i>gra17</i><i>)</i> and novel putative transporter (<i>npt1</i>) double deletion mutant of <i>T</i><i>oxoplasma</i><i> gondii</i> RH strain was engineered. The protective efficacy of vaccination using RH&#916;<i>gra17</i>&#916;<i>npt1</i> tachyzoites against acute, chronic, and congenital toxoplasmosis was studied in a mouse model. Immunization using RH&#916;<i>gra17</i>&#916;<i>npt1 </i>induced a strong humoral and cellular response, as indicated by the increased levels of anti-<i>T</i><i>. gondii</i> specific IgG, interleukin 2 (IL-2), IL-10, IL-12, and interferon-gamma (IFN-&#947;). Vaccinated mice were protected against a lethal challenge dose (10<sup>3</sup> tachyzoites) of wild-type homologous (RH) strain and heterologous (PYS and TgC7) strains, as well as against 100 tissue cysts or oocysts of Pru strain. Vaccination also conferred protection against chronic infection with 10 tissue cysts or oocysts of Pru strain, where the numbers of brain cysts in the vaccinated mice were significantly reduced compared to those detected in the control (unvaccinated + infected) mice. In addition, vaccination protected against congenital infection with 10 <i>T. gondii</i> Pru oocysts (administered orally on day 5 of gestation) as shown by the increased litter size, survival rate and the bodyweight of pups born to vaccinated dams compared to those born to unvaccinated + infected dams. The brain cyst burden of vaccinated dams was significantly lower than that of unvaccinated dams infected with oocysts. Our data show that <i>T. gondii</i> RH&#916;<i>gra17</i>&#916;<i>npt1</i> mutant strain can protect mice against acute, chronic, and congenital toxoplasmosis<i> </i>by balancing inflammatory response with immunogenicity.