Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, Republic of Korea.
Department of Medical Zoology, Kyung Hee University School of Medicine, Seoul, Republic of Korea.
PLoS One. 2019 Aug 29;14(8):e0220865. doi: 10.1371/journal.pone.0220865. eCollection 2019.
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.
尽管数十年来一直在努力开发针对弓形虫感染的疫苗，但目前尚无针对人类的许可疫苗。在发现弓形虫 IMC、ROP18 和 MIC8 中的多个 T 或 B 细胞表位区域后，生成了多抗原 VLPs 或组合 VLPs。用多抗原 VLPs 或组合 VLPs 免疫的小鼠受到弓形虫（ME49）的挑战感染。评估了 T. gondii 特异性 IgG、IgG 同种型和 IgA 抗体反应、记忆 T 和 B 细胞反应和保护作用。通过多抗原 VLPs 疫苗接种，所有感染弓形虫的小鼠均存活。与组合 VLPs 相比，接种疫苗的小鼠在血清中诱导出更高水平的寄生虫特异性 IgG 和 IgG2a 抗体反应、粪便中的 IgA 抗体反应、CD4+和 CD8+T 细胞反应以及细胞因子（IFN-γ、IL-10）反应。特别是，多抗原 VLPs 疫苗接种显示出比组合 VLPs 更高水平的抗体分泌细胞（ASC）反应、CD4+和 CD8+效应记忆 T 细胞和记忆 B 细胞。多抗原 VLPs 疫苗接种显著降低了脑囊泡数量和大小，所有小鼠均存活。表位的预测和分析表明，IMC、ROP18 和 MIC8 显示出针对 T 和 B 细胞的部分重叠表位。我们的结果表明，多抗原 VLPs 疫苗接种诱导的抗体反应、记忆 T 和 B 细胞可能有助于在弓形虫（ME49）挑战感染时完全保护。
