title: Vaccine-induced protection against murine schistosomiasis mansoni with larval excretory-secretory antigens and papain or type-2 cytokines.
abstract: Schistosoma mansoni glyceraldehyde 3-phosphate dehydrogenase (SG3PDH), peroxiredoxin (TPX), and other larval excretory-secretory products (ESP) essentially induce T helper (Th) 1 and Th17 immune responses during a non-protective natural infection. Such an immune environment promotes production of nitric oxide and hydrogen peroxide by interferon-γ-activated monocytes and interleukin (IL)-17-mediated recruitment and activation of neutrophils; however, it also likely prevents engagement of eosinophils and basophils in the hunt for developing larvae. We reasoned that polarizing ESP-induced immune responses toward a Th2 phenotype, via the use of cysteine proteases or type-2 cytokines, would lead to almost total parasite elimination. Accordingly, outbred mice were immunized with 10 μg recombinant SG3PDH and 15 μg TPX-derived peptide together with 10 μg papain, or 200 ng thymic stromal lymphopoietin, IL-25, or IL-33 as an adjuvant. Two weeks later, untreated mice, adjuvant controls, and immunized mice were challenged with 100 or 125 cercariae. Results of 6 experiments indicated that these formulations elicited IgM, IgG1, and IgA specific antibodies, and an increase in ex vivo spleen cells release of IL-4 and IL-5 correlated with highly significant (up to P < 0.0001) reduction of 62 to 78% in challenge worm burden. Improvement of ESP selection, singly or in a combination, and immunization regimen, namely ESP and type-2 cytokine dose and injection site and schedule, could lead to a sterilizing schistosomiasis vaccine in the foreseeable future.
authors.affiliation: Zoology Department, Faculty of Science, Cairo University, Cairo 12613, Egypt. rashika@mailer.eun.eg
authors.forename: Rashika
authors.initials: R
authors.lastname: El Ridi
authors.forename: Hatem
authors.initials: H
authors.lastname: Tallima
mesh_terms: D000276:Adjuvants, Immunologic / Q000145:classification; D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology*; D001700:Biomphalaria; D016207:Cytokines / Q000145:classification / Q000276:immunology*; D005260:Female; D007814:Larva / Q000276:immunology; D008297:Male; D051379:Mice; D010206:Papain / Q000276:immunology*; D012550:Schistosoma mansoni / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000517:prevention & control*; D014612:Vaccines / Q000737:chemistry / Q000592:standards
chemical_list: D000276:Adjuvants, Immunologic; D000947:Antigens, Helminth; D016207:Cytokines; D014612:Vaccines; D010206:Papain