Ahmad Gul, Zhang Weidong, Torben Workineh, Damian Raymond T, Wolf Roman F, White Gary L, Chavez-Suarez Maria, Kennedy Ronald C, Siddiqui Afzal A
Department of Microbiology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, United States.
Vaccine. 2009 May 11;27(21):2830-7. doi: 10.1016/j.vaccine.2009.02.096. Epub 2009 Mar 10.
Schistosomiasis is an important parasitic disease for which there is no available vaccine. We have focused on a functionally important antigen of Schistosoma mansoni, Sm-p80, as a vaccine candidate because of its consistent immunogenicity, protective potential and antifecundity effect observed in murine models; and for its pivotal role in the immune evasion process. In the present study we report that an Sm-p80-based DNA vaccine formulation confers 38% reduction in worm burden in a nonhuman primate model, the baboon (Papio anubis). Animals immunized with Sm-p80-pcDNA3 exhibited a decrease in egg production by 32%. Sm-p80 DNA elicited specific immune responses that include IgG; its subtypes IgG1 and IgG2; and IgM in vaccinated animals. Peripheral blood mononuclear cells (PBMCs) from immunized animals when stimulated in vitro with Sm-p80 produced appreciably more Th1 response enhancing cytokines (IL-2, IFN-gamma) than Th2 response enhancing cytokines (IL-4, IL-10). PBMCs produced appreciably more spot-forming units for INF-gamma than for IL-4 in enzyme-linked immunosorbent spot (ELISPOT) assays. Overall it appears that even though a mixed (Th1/Th2) type of humoral antibody response was generated following immunization with Sm-p80; the dominant protective immune response is Th1 type. These data reinforce the potential of Sm-p80 as an excellent vaccine candidate for schistosomiasis.
血吸虫病是一种重要的寄生虫病,目前尚无可用疫苗。我们聚焦于曼氏血吸虫一种功能上重要的抗原Sm-p80,将其作为疫苗候选物,这是因为在小鼠模型中观察到它具有持续的免疫原性、保护潜力和抗生育作用;并且在免疫逃避过程中发挥关键作用。在本研究中,我们报告了一种基于Sm-p80的DNA疫苗制剂在非人灵长类动物模型狒狒(埃及狒狒)中可使虫负荷降低38%。用Sm-p80-pcDNA3免疫的动物产卵量减少了32%。Sm-p80 DNA在接种动物中引发了包括IgG、其亚型IgG1和IgG2以及IgM在内的特异性免疫反应。免疫动物的外周血单核细胞(PBMCs)在体外受到Sm-p80刺激时,产生的增强Th1反应的细胞因子(IL-2、IFN-γ)明显多于增强Th2反应的细胞因子(IL-4、IL-10)。在酶联免疫吸附斑点(ELISPOT)试验中,PBMCs产生的INF-γ斑点形成单位明显多于IL-4。总体而言,尽管用Sm-p80免疫后产生了混合(Th1/Th2)型的体液抗体反应,但主要的保护性免疫反应是Th1型。这些数据强化了Sm-p80作为血吸虫病优秀疫苗候选物的潜力。