Mbanefo Evaristus Chibunna, Kumagai Takashi, Kodama Yukinobu, Kurosaki Tomoaki, Furushima-Shimogawara Rieko, Cherif Mahamoud Sama, Mizukami Shusaku, Kikuchi Mihoko, Huy Nguyen Tien, Ohta Nobuo, Sasaki Hitoshi, Hirayama Kenji
Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN) and Global COE Program, Nagasaki University, 1-12-4 Sakamoto, 852-8523, Japan; Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, 852-8523, Japan; Department of Parasitology and Entomology, Faculty of Bioscience, Nnamdi Azikiwe University, P.M.B. 5025, Awka, Nigeria.
Section of Environmental Parasitology, Tokyo Medical and Dental University Graduate School of Medical and Dental Science, 113-8519, Japan.
Parasitol Int. 2015 Aug;64(4):24-31. doi: 10.1016/j.parint.2015.01.005. Epub 2015 Jan 17.
There is still urgent need for a vaccine against schistosomiasis, especially in Schistosoma japonicum endemic areas where even a vaccine that will interrupt zoonotic transmission will be potentially effective as an intervention tool. We had developed a novel nanoparticle gene delivery system, which has proven efficacious in gene transfection to target immune cells with complementary adjuvant effect and high protective efficacy in several diseases. Here, we applied this nanoparticle system in combination with S. japonicum glutathione S-transferase (SjGST) DNA vaccine to show the immunogenicity and anti-fecundity effect of the nanoparticle coated vaccine formulation against murine schistosomiasis. The nanoparticle-coated DNA vaccine formulation induced desired immune responses. In comparison with the nanoparticle coated empty vector, it produced significantly increased antigen-specific humoral response, T-helper 1 polarized cytokine environment, higher proportion of IFN-γ producing CD4(+) T-cells and the concomitant decrease in IL-4 producing CD4(+) T-cells. Although there was no effect on worm burden, we recorded a marked reduction in tissue egg burden. There was up to 71.3% decrease in tissue egg burden and 55% reduction in the fecundity of female adult worms. Our data showed that SjGST DNA vaccine, delivered using the nanoparticle gene delivery system, produced anti-fecundity effect on female adult schistosomes as previously described by using conventional subunit vaccine with adjuvant, proving this DNA vaccine formulation as a promising candidate for anti-pathology and transmission blocking application.
仍然迫切需要一种抗血吸虫病疫苗,特别是在日本血吸虫流行地区,即使是一种能够阻断人畜共患病传播的疫苗,作为一种干预工具也可能有效。我们开发了一种新型纳米颗粒基因递送系统,该系统已被证明在基因转染靶向免疫细胞方面有效,具有互补佐剂效应,并在几种疾病中具有高保护效力。在此,我们将这种纳米颗粒系统与日本血吸虫谷胱甘肽S-转移酶(SjGST)DNA疫苗联合应用,以展示纳米颗粒包被疫苗制剂对小鼠血吸虫病的免疫原性和抗繁殖力作用。纳米颗粒包被的DNA疫苗制剂诱导了所需的免疫反应。与纳米颗粒包被的空载体相比,它产生了显著增强的抗原特异性体液反应、辅助性T细胞1极化的细胞因子环境、产生IFN-γ的CD4(+) T细胞比例更高,同时产生IL-4的CD4(+) T细胞减少。虽然对虫体负荷没有影响,但我们记录到组织虫卵负荷显著降低。组织虫卵负荷降低了71.3%,雌虫成虫的繁殖力降低了55%。我们的数据表明,使用纳米颗粒基因递送系统递送的SjGST DNA疫苗对雌虫成虫产生了抗繁殖力作用,这与之前使用传统亚单位疫苗加佐剂所描述的情况一致,证明这种DNA疫苗制剂是抗病理和阻断传播应用的有前途的候选者。