Use of an Sm-p80-Based Therapeutic Vaccine to Kill Established Adult Schistosome Parasites in Chronically Infected Baboons

被引:37
作者
Karmakar, Souvik [1 ,2 ]
Zhang, Weidong [1 ,2 ]
Ahmad, Gul [3 ]
Torben, Workineh [4 ]
Alam, Mayeen U. [1 ,2 ]
Le, Loc [1 ,2 ]
Damian, Raymond T. [5 ]
Wolf, Roman F. [6 ]
White, Gary L. [6 ]
Carey, David W. [6 ]
Carter, Darrick [7 ,8 ]
Reed, Steven G. [7 ]
Siddiqui, Afzal A. [1 ,2 ,9 ,10 ]
机构
[1] Peru State Coll, Ctr Trop Med & Infect Dis, Sch Arts & Sci, Peru, NE USA
[2] Peru State Coll, Dept Mol Microbiol & Immunol, Sch Arts & Sci, Peru, NE USA
[3] Peru State Coll, Dept Nat Sci, Sch Arts & Sci, Peru, NE USA
[4] Tulane Natl Primate Res Ctr, Covington, LA USA
[5] Univ Georgia, Dept Cellular Biol, Athens, GA 30602 USA
[6] Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA
[7] Infect Dis Res Inst, Seattle, WA USA
[8] PAI Life Sci, Seattle, WA USA
[9] Texas Tech Univ, Hlth Sci Ctr, Dept Internal Med, Lubbock, TX 79430 USA
[10] Texas Tech Univ, Hlth Sci Ctr, Dept Pathol, Lubbock, TX 79430 USA
基金
美国国家卫生研究院;
关键词
Schistosomiasis; Schistosoma mansoni; Sm-p80; calpain; therapeutic vaccine; nonhuman primate; baboon; NEGLECTED TROPICAL DISEASES; NEUTRAL PROTEASE CALPAIN; NONHUMAN PRIMATE MODEL; DNA VACCINE; HELMINTH DISEASES; MANSONI INFECTION; IMMUNE-RESPONSE; RESEARCH AGENDA; PROTECTION; RESISTANCE;
D O I
10.1093/infdis/jiu031
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
No vaccines are available for human use for any parasitic infections, including the helminthic disease schistosomiasis. Sm-p80, the large subunit of Schistosoma mansoni calpain, is a leading antigen candidate for a schistosomiasis vaccine. Prophylactic and antifecundity efficacies of Sm-p80 have been tested using a variety of vaccine approaches in both rodent and nonhuman primate models. However, the therapeutic efficacy of a Sm-p80-based vaccine had not been determined. In this study, we evaluated the therapeutic efficacy of Smp-80 by using 2 different strategies and 3 Sm-p80-based vaccine formulations in baboons. Vaccine formulations were able to decrease established adult worms by 10%-36%, reduce retention of eggs in tissues by 10%-57%, and decrease egg excretion in feces by 13%-33%, compared with control formulations. Marked differences were observed in B and T cell immune correlates between vaccinated and control animals. This is the first report of killing of established adult schistosome worms by a vaccine. In addition to distinct prophylactic efficacy of Sm-p80, this study adds to the evidence that Sm-p80 is a potentially important antigen with both substantial prophylactic and therapeutic efficacies. These data reinforce that Sm-p80 should be moved forward along the path toward human clinical trials.
引用
收藏
页码:1929 / 1940
页数:12
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