Schistosoma Mansoni Antigen Sm-p80: Prophylactic Efficacy using TLR4 Agonist Vaccine Adjuvant Glucopyranosyl Lipid A-Alum in Murine and Non-Human Primate Models. (December 2018)

• Record Type: Journal Article
• Authors: Zhang, Weidong; Ahmad, Gul; Molehin, Adebayo J; Torben, Workineh; Le, Loc; Kim, Eunjee; Lazarus, Samra; Siddiqui, Arif J; Carter, Darrick; Siddiqui, Afzal A
• Is Part Of: Journal of investigative medicine. Volume 66:Number 8(2018)
• Page Start: 1124
• Page End: 1132
• Publication Date: 2018-12
• Subjects: biomedical research -- disease models -- animal -- enzyme-linked immunosorbent assay -- immunization -- innate immune response; Clinical medicine -- Periodicals; Medicine -- Research -- Periodicals; Medicine; Research -- United States; Clinical medicine; Medicine -- Research; Periodicals; 616.075
• DOI: 10.1136/jim-2018-000786
• Languages: English
• ISSNs: 1081-5589

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.