Resistance to Chronic<i>Toxoplasma gondii</i>Infection Induced by a DNA Vaccine Expressing GRA16

Abstract

Toxoplasma gondii can infect all warm-blooded animals including human beings. T. gondii dense granule protein 16 (TgGRA16) as a crucial virulence factor could modulate the host gene expression. Here, a DNA vaccine expressing TgGRA16 was constructed to explore the protective efficacy against T. gondii infection in Kunming mice. The immune responses induced by pVAX-GRA16 were also evaluated. Mice immunized with pVAX-GRA16 could elicit higher levels of specific IgG antibody and strong cellular response compared to those in controls. The DNA vaccination significantly increased the levels of cytokines (IFN-<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mrow><mml:mi>γ</mml:mi></mml:mrow></mml:math>, IL-2, IL-4, and IL-10) and the percentages of CD4+ and CD8+ T cells in mice. After lethal challenge, mice immunized with pVAX-GRA16 (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mn fontstyle="italic">8.4</mml:mn><mml:mo>±</mml:mo><mml:mn fontstyle="italic">0.78</mml:mn></mml:math>days) did not show a significant longer survival time than that in controls (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M3"><mml:mn fontstyle="italic">7.1</mml:mn><mml:mo>±</mml:mo><mml:mn fontstyle="italic">0.30</mml:mn></mml:math>days) (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M4"><mml:mi>p</mml:mi><mml:mo>&gt;</mml:mo><mml:mn fontstyle="italic">0.05</mml:mn></mml:math>). However, in chronic toxoplasmosis model (administration of 10 brain cysts of PRU strain orally), numbers of tissue cysts in mice immunized with pVAX-GRA16 were significantly reduced compared to those in controls (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M5"><mml:mi>p</mml:mi><mml:mo>&lt;</mml:mo><mml:mn fontstyle="italic">0.05</mml:mn></mml:math>) and the rate of reduction could reach 43.89%. The results indicated that the TgGRA16 would be a promising vaccine candidate for further development of effective epitope-based vaccines against chronic T. gondii infection in mice.