title: Preclinical prophylactic efficacy testing of Sm-p80-based vaccine in a nonhuman primate model of Schistosoma mansoni infection and immunoglobulin G and E responses to Sm-p80 in human serum samples from an area where schistosomiasis is endemic.
abstract: The prophylactic efficacy of a schistosome antigen (Sm-p80) was tested in a nonhuman primate model, the baboon. Using a total of 28 baboons, different vaccination strategies were used including recombinant Sm-p80 protein formulated in Toll-like receptor 7 and Toll-like receptor 9 agonists, and DNA priming followed by boosting with protein plus adjuvants. Recombinant protein approaches provided levels of prophylactic efficacy of 52%-58%, whereas prime-boost approaches conferred 38%-47% protection in baboons. An appropriately balanced pro-inflammatory (T-helper 17 [Th17] and Th1) and anti-inflammatory (Th2) type of response was generated; the Th1 and Th17 types of immune responses appear to be indicative of increased prophylactic efficacy. Production and expression of several cytokines (interleukin 2 [IL-2], interferon γ, IL-12α, IL-1β, IL-6, and IL-22) were up-regulated in vaccinated animals. Human correlate studies revealed Sm-p80 reactivity with immunoglobulin G in human serum samples from schistosome-infected individuals. In addition, a complete lack of prevailing Sm-p80-specific immunoglobulin E in a high-risk or infected population was observed, thus minimizing the risk of hypersensitivity reaction following vaccination with Sm-p80 in humans. This study provided the proof of concept to move Sm-p80 forward into further preclinical development leading to human clinical trials.
authors.affiliation: Department of Microbiology and Immunology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
authors.forename: Gul
authors.initials: G
authors.lastname: Ahmad
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhang
authors.forename: Workineh
authors.initials: W
authors.lastname: Torben
authors.forename: Afzal
authors.initials: A
authors.lastname: Ahrorov
authors.forename: Raymond T
authors.initials: RT
authors.lastname: Damian
authors.forename: Roman F
authors.initials: RF
authors.lastname: Wolf
authors.forename: Gary L
authors.initials: GL
authors.lastname: White
authors.forename: David W
authors.initials: DW
authors.lastname: Carey
authors.forename: Pauline N M
authors.initials: PN
authors.lastname: Mwinzi
authors.forename: Lisa
authors.initials: L
authors.lastname: Ganley-Leal
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Kennedy
authors.forename: Afzal A
authors.initials: AA
authors.lastname: Siddiqui
mesh_terms: D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood*; D000947:Antigens, Helminth / Q000008:administration & dosage / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D019353:Endemic Diseases; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D010215:Papio; D018419:Primate Diseases / Q000276:immunology / Q000517:prevention & control; D012550:Schistosoma mansoni / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000517:prevention & control*; D044967:Serum / Q000276:immunology; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D016207:Cytokines; D007074:Immunoglobulin G; D019444:Vaccines, DNA; D022223:Vaccines, Subunit; D007073:Immunoglobulin E