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

被引:54
作者
Ahmad, Gul [1 ]
Zhang, Weidong [1 ]
Torben, Workineh [1 ]
Damian, Raymond T. [2 ]
Wolf, Roman F. [3 ]
White, Gary L. [3 ]
Chavez-Suarez, Maria [3 ]
Kennedy, Ronald C. [1 ]
Siddiqui, Afzal A. [1 ,4 ]
机构
[1] Texas Tech Univ, Hlth Sci Ctr, Dept Microbiol & Immunol, Lubbock, TX 79430 USA
[2] Univ Georgia, Dept Cellular Biol, Athens, GA 30602 USA
[3] Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK 73104 USA
[4] Texas Tech Univ, Hlth Sci Ctr, Dept Internal Med, Lubbock, TX 79430 USA
关键词
DNA vaccination; Schistosomiasis; Schistosoma mansoni; Sm-p80; Calpain; Nonhuman primate; Baboons; NEUTRAL PROTEASE CALPAIN; BABOON PAPIO-ANUBIS; LARGE SUBUNIT; IMMUNE-RESPONSE; OLIVE BABOON; ADULT WORMS; RECOMBINANT; JAPONICUM; INFECTION; RESISTANCE;
D O I
10.1016/j.vaccine.2009.02.096
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 all 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 all excellent vaccine candidate for schistosomiasis. (C) 2009 Elsevier Ltd. All rights reserved.
引用
收藏
页码:2830 / 2837
页数:8
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