Virus-like particles containing multiple antigenic proteins of Toxoplasma gondii induce memory T cell and B cell responses

Abstract

Although the efforts to develop vaccine against Toxoplasma gondii infection were made for decades, there is currently no licensed vaccine available for humans. Upon discovering a number of T or B cell epitope regions from T . gondii IMC, ROP18 and MIC8, multi-antigen VLPs or combination VLPs were generated. Mice immunized with multi-antigen VLPs or combination VLPs were challenge infected with T . gondii (ME49). T . gondii -specific IgG, IgG isotypes and IgA antibody responses, memory T and B cell responses and protection were evaluated. All the mice survived upon T . gondii challenge infection by multi-antigen VLPs vaccination. Vaccinated mice elicited higher levels of parasite-specific IgG and IgG2a antibody responses in sera, IgA antibody responses in feces, CD4 + and CD8 + T cell responses, and cytokines (IFN-γ, IL-10) responses compared to combination VLPs. In particular, the multi-antigen VLPs vaccination showed significantly higher levels of antibody secreting cell (ASC) responses, CD4 + and CD8 + effector memory T cells, and memory B cells than combination VLPs. Multi-antigen VLPs vaccination showed significant reduction of brain cyst counts and size, and all mice survived. Prediction and analysis of epitopes have indicated that IMC, ROP18 and MIC8 showed partially overlapping epitopes for T and B cells. Our results indicated that antibody responses, memory T and B cells induced by multi-antigen VLPs vaccination might contribute to the complete protection upon T . gondii (ME49) challenge infection.

Evaluation of CpG-ODN-Adjuvanted Toxoplasma gondii Virus-Like Particle Vaccine upon One, Two, and Three Immunizations

“…TG146 VLP vaccine expressing T. gondii IMC, ROP18, and MIC8 was produced in insect cells as described previously [ 18 , 20 ]. The multi-antigenic TG146 VLPs were aliquoted and stored at −80 °C until use.…”

“…T. gondii -specific antibody and cytokine levels were determined by ELISA as reported previously [ 18 , 26 ]. Diluted immune sera (1:100), urine (1:3), vaginal samples (1:3), fecal supernatants (1:3), intestine samples (1:100), and brain supernatants (undiluted) were used as primary antibodies.…”

“…Though the protective efficacies of the live attenuated vaccines appear promising, the safety aspects of these vaccines are of concern since attenuated T. gondii can revert to the highly pathogenic wild type [ 14 ]. As a safer alternative, we generated several virus-like particle (VLP) T. gondii vaccines conferring 100% protection against a lethal dose of T. gondii ME49 strain in mice [ 17 , 18 , 19 , 20 ]. Although all of the immunized mice survived in our previous studies, incomplete removal of cerebral cysts and bodyweight loss upon challenge infection from these mice indicated that further improvements to the VLP vaccines are needed to minimize disease manifestation.…”

Toxoplasma gondii virus‐like particle vaccination alleviates inflammatory response in the brain upon T gondii infection

“…In spite of these efforts, vaccine incorporating the aforementioned strategies failed to provide sufficient protection in mice. Contrastingly, our previous works have demonstrated that virus‐like particles (VLPs) vaccines expressing various T gondii proteins could provide adequate protection against T gondii ME49 in murine models 9‐11 . However, reduced inflammatory responses in the brain induced by VLPs immunization upon T gondii ME49 infection has not been investigated in any of the previous works.…”

Virus‐like particles expressing Plasmodium berghei MSP‐8 induce protection against P. berghei infection

“…Since nonspecific protective effects of vaccination can be induced as in the case with P. yoelli,26 further studies are needed. Expression of the surface proteins IgG1 and CD27 was used to gate memory B cells as these have been defined in several bacterial, viral and parasitic infections 27,28. MSP-8 VLPs immunization showed a significant increase in the frequencies and the total numbers of IgG1 + CD27 high B cells in the spleen.PvMSP8 has been shown to be immunogenic in natural P. vivax infections and produces both cell-mediated and antibody-mediated immunity 21.…”