Protective and antifecundity effects of Sm-p80-based DNA vaccine formulation against Schistosoma mansoni in a nonhuman primate model.
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.
Ahmad
Gul
G
Department of Microbiology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, United States.
Zhang
Weidong
W
Torben
Workineh
W
Damian
Raymond T
RT
Wolf
Roman F
RF
White
Gary L
GL
Chavez-Suarez
Maria
M
Kennedy
Ronald C
RC
Siddiqui
Afzal A
AA
D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D000947:Antigens, Helminth / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D005298:Fertility; D008297:Male; D023421:Models, Animal; D010063:Ovum / Q000276:immunology; D010215:Papio / Q000276:immunology*; D012550:Schistosoma mansoni / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012555:Schistosomiasis mansoni / Q000276:immunology / Q000517:prevention & control*; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*
D000913:Antibodies, Protozoan; D000947:Antigens, Helminth; D016207:Cytokines; D019444:Vaccines, DNA