Literature DB >> 24436452

Use of an Sm-p80-based therapeutic vaccine to kill established adult schistosome parasites in chronically infected baboons.

Souvik Karmakar1, Weidong Zhang1, Gul Ahmad2, Workineh Torben3, Mayeen U Alam1, Loc Le1, Raymond T Damian4, Roman F Wolf5, Gary L White5, David W Carey5, Darrick Carter6, Steven G Reed7, Afzal A Siddiqui8.   

Abstract

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 Sm-p80 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.
© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Entities:  

Keywords:  Schistosoma mansoni; Schistosomiasis; Sm-p80; baboon; calpain; nonhuman primate; therapeutic vaccine

Mesh:

Substances:

Year:  2014        PMID: 24436452      PMCID: PMC4038147          DOI: 10.1093/infdis/jiu031

Source DB:  PubMed          Journal:  J Infect Dis        ISSN: 0022-1899            Impact factor:   5.226


  50 in total

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  20 in total

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3.  Sm-p80-based schistosomiasis vaccine: double-blind preclinical trial in baboons demonstrates comprehensive prophylactic and parasite transmission-blocking efficacy.

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Review 4.  Development of a schistosomiasis vaccine.

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5.  Longevity of Sm-p80-specific antibody responses following vaccination with Sm-p80 vaccine in mice and baboons and transplacental transfer of Sm-p80-specific antibodies in a baboon.

Authors:  Weidong Zhang; Gul Ahmad; Loc Le; Juan U Rojo; Souvik Karmakar; Kory A Tillery; Workineh Torben; Raymond T Damian; Roman F Wolf; Gary L White; David W Carey; Darrick Carter; Steven G Reed; Afzal A Siddiqui
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6.  Cross-species prophylactic efficacy of Sm-p80-based vaccine and intracellular localization of Sm-p80/Sm-p80 ortholog proteins during development in Schistosoma mansoni, Schistosoma japonicum, and Schistosoma haematobium.

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10.  Of monkeys and men: immunomic profiling of sera from humans and non-human primates resistant to schistosomiasis reveals novel potential vaccine candidates.

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