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Mast cell activator compound 48/40 is not an effective adjuvant for UV-attenuated Toxoplasma gondii vaccine
Xi Li1,2, Shengjie Chen1,2, Shiguang Huang3
1Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China.
Abstract:
Toxoplasma gondii (T. gondii, Tg) is a globally distributed parasitic protozoan causing different forms of toxoplasmosis in humans. Mast cells (MCs) play a role during T. gondii infection. Several studies suggest that MC activator compound 48/80 (C48/80) may be an effective vaccine adjuvant resulting in a potent and protective antigen-specific immune response against bacteria or virus infections. The present study was performed to determine whether C48/80 had adjuvant activity for ultraviolet (UV)-attenuated T. gondii vaccine to induce protective immune responses against T. gondii in mouse model. Kunming mice were divided into the following groups: naive mice, naive mice administrated with C48/80 intraperitoneal (i.p.) injection, mice infected by i.p. injection of 104 T. gondii RH strain alone (Tg group), mice infected with 104 RH tachyzoites plus C48/80 administration (Tg + C48/80), mice immunized with UV-Tg alone, and mice immunized with UV-Tg plus C48/80 administration (UV-Tg + C48/80). All the vaccinated mice were challenged with 104 tachyzoites of T. gondii RH strain at the same time as the primary infection. The survival rates, liver histopathologies, liver parasite burdens, and mRNA expression levels of Th1 and Th2 cytokines in the livers and spleens detected by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) were compared among the aforementioned groups after primary infection or challenge infection. The results showed that, compared to the Tg group or Tg + C48/80 group, the UV-Tg + Tg group and UV-Tg + C48/80 + Tg group had significantly prolonged survival time, lower liver histopathological scores, decreased liver parasite burdens, and increased levels of Th1 and Th2 cytokines in the livers and spleens. There was no significant difference of survival time between the UV-Tg + Tg group and the UV-Tg + C48/80 + Tg group; however, the UV-Tg + C48/80 + Tg group showed higher parasite burden, more severe liver histopathology, and decreased IL-4 level compared to the UV-Tg + Tg group. These results indicate that C48/80 had no adjuvant activity for the immunization induced by UV-attenuated T. gondii vaccine.
Insights
Compound 48/80 (C48/80) did not enhance the immune response of an ultraviolet-attenuated Toxoplasma gondii (UV-Tg) vaccine in mice. The UV-Tg vaccine alone provided protection, but adding C48/80 did not improve survival or reduce parasite burden.
Area of Science:
- Immunology
- Parasitology
- Vaccinology
Background:
- Toxoplasma gondii (T. gondii) is a widespread parasite causing toxoplasmosis.
- Mast cells (MCs) are involved in T. gondii infections.
- Compound 48/80 (C48/80) is a potential vaccine adjuvant.
Purpose of the Study:
- To evaluate if C48/80 enhances the efficacy of an ultraviolet-attenuated T. gondii (UV-Tg) vaccine.
- To assess the protective immune response induced by UV-Tg vaccine with or without C48/80 in a mouse model.
Main Methods:
- Mice were grouped and administered with T. gondii, C48/80, UV-Tg vaccine, or combinations.
- Groups were challenged with T. gondii, and outcomes including survival, liver pathology, parasite load, and cytokine expression were analyzed.
- Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) was used to measure Th1 and Th2 cytokine mRNA levels.
Main Results:
- Both UV-Tg alone and UV-Tg with C48/80 groups showed improved survival, reduced liver pathology, and lower parasite burden compared to T. gondii infection alone.
- No significant difference in survival was observed between UV-Tg alone and UV-Tg with C48/80 groups.
- The UV-Tg with C48/80 group exhibited higher parasite burden, more severe liver damage, and reduced IL-4 levels compared to the UV-Tg alone group.
Conclusions:
- C48/80 did not demonstrate adjuvant activity for the UV-Tg vaccine.
- The UV-Tg vaccine alone conferred protective immunity against T. gondii challenge.
- C48/80 may potentially impair the immune response induced by the UV-Tg vaccine.
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