Schistosoma mansoni antigen Sm-p80: prophylactic efficacy using TLR4 agonist vaccine adjuvant glucopyranosyl lipid A-Alum in murine and non-human primate models.

Abstract

Sm-p80, the large subunit of Schistosoma mansoni calpain, is a leading candidate for a schistosomiasis vaccine. The prophylactic and antifecundity efficacy of Sm-p80 has been tested in three animal models (mouse, hamster and baboon) using a multitude of vaccine formulations and approaches. In our continual effort to enhance the vaccine efficacy, in this study, we have utilized the adjuvant, synthetic hexa-acylated lipid A derivative, glucopyranosyl lipid A (GLA) formulated in aluminum (GLA-Alum) with recombinant Sm-p80. The rSm-p80+GLA-Alum immunization regimen provided 33.33%-53.13% reduction in worm burden in the mouse model and 38% worm burden reduction in vaccinated baboons. Robust Sm-p80-specific immunoglobulin (Ig)G, IgG1, IgG2a and IgM responses were observed in all immunized animals. The rSm-p80+GLA-Alum coadministration induced a mix of T-helper (Th) cells (Th1, Th2 and Th17) responses as determined via the release of interleukin (IL)-2, IL-4, IL-18, IL-21, IL-22 and interferon-γ.

• Authors: Weidong Zhang, Gul Ahmad, Adebayo J Molehin, Workineh Torben, Loc Le, Eunjee Kim, Samra Lazarus, Arif J Siddiqui, Darrick Carter, Afzal A Siddiqui
• Journal: Journal of investigative medicine : the official publication of the American Federation for Clinical Research (J Investig Med) Vol. 66 Issue 8 Pg. 1124-1132 (12 2018) ISSN: 1708-8267 [Electronic] England
• PMID: 29997146 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © American Federation for Medical Research (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Chemical References

• Adjuvants, Immunologic
• Alum Compounds
• Antigens, Helminth
• Cytokines
• Glucosides
• Lipid A
• RNA, Messenger
• Recombinant Proteins
• Toll-Like Receptor 4
• Vaccines
• glucopyranosyl lipid-A
• aluminum sulfate

Topics

• Adjuvants, Immunologic (pharmacology)
• Alum Compounds (pharmacology)
• Animals
• Antigens, Helminth (immunology)
• Cell Proliferation
• Cytokines (biosynthesis, genetics)
• Female
• Glucosides (immunology)
• Immunity, Humoral
• Lipid A (immunology)
• Mice, Inbred C57BL
• Papio
• RNA, Messenger (genetics, metabolism)
• Recombinant Proteins (metabolism)
• Schistosoma mansoni (immunology)
• Schistosomiasis mansoni (immunology, parasitology)
• T-Lymphocytes, Helper-Inducer (immunology)
• Toll-Like Receptor 4 (agonists)
• Vaccination
• Vaccines (immunology)