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

Su-Hwa Lee,Hae-Ji Kang,Ki-Back Chu,Fu-Shi Quan,Paulo Lee Ho

doi:10.1371/journal.pone.0220865

Su-Hwa Lee, Hae-Ji Kang + Show 3 more

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https://doi.org/10.1371/journal.pone.0220865

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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.

Highlights

Toxoplasma gondii, a notorious protozoan parasite belonging to the phylum Apicomplexa, is capable of infecting virtually all vertebrate hosts using various transmission routes to cause the zoonotic disease toxoplasmosis [1,2]
In this study, we report the memory T and B responses, T or B cell epitopes, antibody secreting cell (ASC) responses and protections induced by multi-antigen virus-like particles (VLPs) and combination VLPs upon T. gondii ME49 challenge infections in mice
To evaluate the level of T. gondii-specific antibody induced by multi-antigen VLPs or combination VLPs vaccines, we measured the IgG, IgG1 and IgG2a antibody responses in serum and measured the IgA antibody responses in feces upon challenge (Fig 2)

Summary

Introduction

Toxoplasma gondii, a notorious protozoan parasite belonging to the phylum Apicomplexa, is capable of infecting virtually all vertebrate hosts using various transmission routes to cause the zoonotic disease toxoplasmosis [1,2]. Therapeutic regimen for human toxoplasmosis requires the use of pyrimethamine and sulfadiazine, but side effects and insufficient efficacies against non-tachyzoite stages of the parasite limits their use [4]. Toxovax is currently the only available commercial toxoplasmosis vaccine, albeit being limited to veterinary use with arising safety concerns [5]. These issues, combined with other detriments associated with the treatment, may have created an impetus for the development of a novel vaccine which could effectively block and control the transmission of toxoplasmosis

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