Kang Hae-Ji, Lee Su-Hwa, Kim Min-Ju, Chu Ki-Back, Lee Dong-Hun, Chopra Manika, Choi Hyo-Jick, Park Hyunwoo, Jin Hui, Quan Fu-Shi
Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Korea.
Department of Chemical and Materials Engineering, University of Alberta, Edmonton, AB T6G 2V4, Canada.
Pharmaceutics. 2019 Jul 16;11(7):342. doi: 10.3390/pharmaceutics11070342.
Rhoptry organelle proteins (ROPs) secreted by () play a critical role during parasite invasion into host cells. In this study, virus-like particles (VLPs) vaccines containing ROP4 and/or ROP13 together with influenza M1 were generated. ROP4+ROP13 VLPs were produced by combining ROP4 VLPs with ROP13 VLPs, and ROP(4 + 13) VLPs by co-infecting insect cells with recombinant baculovirus expressing ROP4 or ROP13. Mice intranasally immunized with ROP(4 + 13) VLPs showed significantly higher levels of IgG, IgG1, IgG2a and IgA antibody responses in sera compared to ROP4+ROP13VLPs. Upon challenge infection by oral route, mice immunized with ROP(4 + 13) VLPs elicited higher levels of IgG and IgA antibody responses in fecal, urine, intestine and vaginal samples as well as CD4 T, CD8 T cells, and germinal center B cell responses compared to other type of vaccines, ROP4 VLPs, ROP13 VLPs, and ROP4+ROP13 VLPs. ROP(4 + 13) VLPs vaccination showed a significant decrease in the size and number of cyst in the brain and less body weight loss compared to combination ROP4+ROP13 VLPs upon challenge infection with ME49. These results indicated that the ROP(4 + 13) VLPs vaccination provided enhanced protection against infection compared to ROP4+ROP13 VLPs, providing an important insight into vaccine design strategy for VLPs vaccines.
（）分泌的棒状体细胞器蛋白（ROPs）在寄生虫侵入宿主细胞过程中起关键作用。在本研究中，制备了包含ROP4和/或ROP13以及流感M1的病毒样颗粒（VLPs）疫苗。ROP4 + ROP13 VLPs通过将ROP4 VLPs与ROP13 VLPs组合产生，而ROP(4 + 13) VLPs则通过用表达ROP4或ROP13的重组杆状病毒共感染昆虫细胞产生。与ROP4 + ROP13 VLPs相比，经ROP(4 + 13) VLPs鼻内免疫的小鼠血清中IgG、IgG1、IgG2a和IgA抗体反应水平显著更高。经口途径进行攻击感染后，与其他类型的疫苗（ROP4 VLPs、ROP13 VLPs和ROP4 + ROP13 VLPs）相比，经ROP(4 + 13) VLPs免疫的小鼠在粪便、尿液、肠道和阴道样本中引发了更高水平的IgG和IgA抗体反应以及CD4 T、CD8 T细胞和生发中心B细胞反应。在用ME49进行攻击感染后，与ROP4 + ROP13 VLPs组合相比，ROP(4 + 13) VLPs疫苗接种显示脑中囊肿的大小和数量显著减少，体重减轻也更少。这些结果表明，与ROP4 + ROP13 VLPs相比，ROP(4 + 13) VLPs疫苗接种提供了更强的针对感染的保护，为VLPs疫苗的疫苗设计策略提供了重要见解。
