Protective and antifecundity effects of Sm-p80-based DNA vaccine formulation against Schistosoma mansoni in a nonhuman primate model.

Protective and antifecundity effects of Sm-p80-based DNA vaccine formulation against Schistosoma mansoni in a nonhuman primate model.
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DOI:
10.1016/j.vaccine.2009.02.096
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发表时间:
2009-05-11
期刊:
影响因子:
5.5
通讯作者:
Siddiqui AA
Siddiqui AA
中科院分区:
医学3区
文献类型:
--
作者:
Ahmad G;Zhang W;Torben W;Damian RT;Wolf RF;White GL;Chavez-Suarez M;Kennedy RC;Siddiqui AA

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血吸虫病是一种重要的寄生虫病,目前尚无疫苗。我们一直专注于曼氏血吸虫,Sm-p80,作为候选疫苗的功能上重要的抗原,因为其一致的免疫原性,保护潜力和抗生育作用在小鼠模型中观察到的,并在免疫逃避过程中发挥关键作用。在本研究中,我们报告说,Sm-p80为基础的DNA疫苗配方赋予38%的减少蠕虫负担的非人灵长类动物模型,狒狒(Papio anubis)。用Sm-p80-pcDNA 3免疫的动物表现出产蛋减少32%。Sm-p80 DNA在接种疫苗的动物中引起特异性免疫应答,包括IgG;其亚型IgG 1和IgG 2;和IgM。Sm-p80体外刺激免疫动物的外周血单个核细胞(PMBCs)产生的Th 1应答增强细胞因子(IL-2、IFN-γ)明显多于Th 2应答增强细胞因子(IL-4、IL-10)。在酶联免疫吸附斑点(ELISPOT)试验中,PBMC产生的INF-γ斑点形成单位明显多于IL-4。总的来说,尽管Sm-p80免疫后产生了混合型(Th 1/Th 2)体液抗体应答,但主要的保护性免疫应答是Th 1型。这些数据加强了Sm-p80作为血吸虫病优秀候选疫苗的潜力。
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 a 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 (PMBCs) from immunized animals when stimulated in vitro with Sm-p80 produced appreciably more Th1 response enhancing cytokines (IL-2, IFN-γ) than Th2 response enhancing cytokines (IL-4, IL-10). PBMCs produced appreciably more spot forming units for INF-γ 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.
DOI: 10.1016/s0264-410x(97)00081-9
发表时间: 1997-10-01
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