title: Schistosomiasis vaccine candidate Sm14/GLA-SE: Phase 1 safety and immunogenicity clinical trial in healthy, male adults.
abstract: METHODS
  Safety and immunogenicity of a recombinant 14kDa, fatty acid-binding protein(FABP) from Schistosoma mansoni (rSm14) were evaluated through an open, non-placebo-controlled, dose-standardized trial, performed at a single research site. The vaccine was formulated with glucopyranosyl lipid A (GLA) adjuvant in an oil-in-water emulsion (SE) and investigated in 20 male volunteers from a non-endemic area for schistosomiasis in the state of Rio de Janeiro, Brazil. Fifty microgram rSm14 with 10 μg GLA-SE (rSm14/GLA-SE)/dose were given intramuscularly three times with 30-day intervals. Participants were assessed clinically, biochemically and immunologically for up to 120 days.
  
  
  METHODS
  Participants were screened for inclusion by physical examination, haematology and blood chemistry; then followed to assess adverse events and immunogenicity. Sera were tested for IgG (total and isotypes) and IgE. T cell induction of cytokines IL-2, IL-5, IL-10, IFNγ and TNFα was assessed by Milliplex kit and flow cytometry.
  
  
  RESULTS
  The investigational product showed high tolerability; some self-limited, mild adverse events were observed during and after vaccine administration. Significant increases in Sm14-specific total IgG, IgG1 and IgG3 were observed 30 days after the first vaccination with specific IgG2 and IgG4 after 60 days. An increase in IgE antibodies was not observed at any time point. The IgG response was augmented after the second dose and 88% of all vaccinated subjects had developed high anti-Sm14 IgG titres 90 days after the first injection. From day 60 and onwards, there was an increase in CD4(+) T cells producing single cytokines, particularly TNFα and IL-2, with no significant increase of multi-functional TH1 cells.
  
  
  CONCLUSIONS
  Clinical trial data on tolerability and specific immune responses after vaccination of adult, male volunteers in a non-endemic area for schistosomiasis with rSm14/GLA-SE, support this product as a safe, strongly immunogenic vaccine against schistosomiasis paving the way for follow-up Phase 2 trials. Study registration ID: NCT01154049 at http://www.clinicaltrials.gov.
authors.affiliation: Instituto Nacional de Infectologia Evandro Chagas (INI), Fiocruz, Av. Brasil, No. 4365, Manguinhos, Rio de Janeiro, 21045-900, Brazil.
authors.forename: Marilia
authors.initials: M
authors.lastname: Santini-Oliveira
authors.affiliation: Infectious Disease Research Institute (IDRI), 1616, Eastlake Ave E, Suite 400, Seattle, WA 98102, USA.
authors.forename: Rhea N
authors.initials: RN
authors.lastname: Coler
authors.affiliation: Fiocruz/MS, Rua Gabriel Abrão s/n, Jardim das Nações, Campo Grande, Mato Grosso do Sul, 79.081-746, Brazil.
authors.forename: Juçara
authors.initials: J
authors.lastname: Parra
authors.affiliation: Instituto Nacional de Infectologia Evandro Chagas (INI), Fiocruz, Av. Brasil, No. 4365, Manguinhos, Rio de Janeiro, 21045-900, Brazil.
authors.forename: Valdilea
authors.initials: V
authors.lastname: Veloso
authors.affiliation: Infectious Disease Research Institute (IDRI), 1616, Eastlake Ave E, Suite 400, Seattle, WA 98102, USA.
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Jayashankar
authors.affiliation: Laboratório de Esquistossomose Experimental, Instituto Oswaldo Cruz, Fiocruz, Av. Brasil, No. 4365, Manguinhos, 21045-900 Rio de Janeiro, Brazil.
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Pinto
authors.affiliation: Department of Rehabilitation Medicine, School of Medicine, University of Washington, 1959 NE Pacific St, UW Box 356490, Seattle, WA 98195-6490, USA.
authors.forename: Marcia A
authors.initials: MA
authors.lastname: Ciol
authors.affiliation: Geospatial Health, Ingerod 407, S-45494 Brastad, Sweden.
authors.forename: Robert
authors.initials: R
authors.lastname: Bergquist
authors.affiliation: Infectious Disease Research Institute (IDRI), 1616, Eastlake Ave E, Suite 400, Seattle, WA 98102, USA.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Reed
authors.affiliation: Laboratório de Esquistossomose Experimental, Instituto Oswaldo Cruz, Fiocruz, Av. Brasil, No. 4365, Manguinhos, 21045-900 Rio de Janeiro, Brazil. Electronic address: mtendler@ioc.fiocruz.br.
authors.forename: Miriam
authors.initials: M
authors.lastname: Tendler
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000293:Adolescent; D000328:Adult; D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood; D001938:Brazil; D016207:Cytokines / Q000276:immunology; D050556:Fatty Acid-Binding Proteins / Q000276:immunology*; D015801:Helminth Proteins / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D012550:Schistosoma mansoni; D012552:Schistosomiasis / Q000517:prevention & control*; D013601:T-Lymphocytes / Q000276:immunology; D014612:Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000909:Antibodies, Helminth; D016207:Cytokines; D050556:Fatty Acid-Binding Proteins; D015801:Helminth Proteins; D007074:Immunoglobulin G; D014612:Vaccines
keywords: Brazil; Fatty acid-binding protein (FABP); GLA-SE; Phase 1 clinical trial; Recombinant vaccine; Schistosomiasis; rSm14