title: The impact of concurrent and treated Ancylostoma ceylanicum hookworm infections on the immunogenicity of a recombinant hookworm vaccine in hamsters.
abstract: BACKGROUND
  The effect of concurrent (active) and treated hookworm infections on the immunogenicity of vaccination with the recombinant fusion protein Ay-Ancylostoma-secreted protein 2 was analyzed in the Golden Syrian hamster.
  
  
  METHODS
  Hamsters were infected with the hookworm Ancylostoma ceylanicum and vaccinated with the recombinant protein, with Quil A used as adjuvant. As controls, hookworm-infected hamsters were treated with the anthelmintic drug pyrantel pamoate before vaccination. Naive hamsters (i.e., those with neither previous hookworm infections nor treatment) were also vaccinated.
  
  
  RESULTS
  The proliferation capacities of carboxyfluorescein diacetate succinimidyl ester-positive lymphocytes from the hookworm-infected vaccinated group were reduced by 50% relative to the capacities of lymphocytes from uninfected or treated vaccinated hamsters; capacities were comparable to the rates observed in lymphocytes from the hamsters vaccinated with the adjuvant alone. Immunoglobulin G1 antibody responses were also reduced in the actively infected, untreated hamsters, and interferon- gamma and interleukin-4 cytokine mRNAs were down-regulated. Conversely, interleukin-10 and tumor necrosis factor- alpha mRNAs were up-regulated in those hamsters.
  
  
  CONCLUSIONS
  These results suggest that hookworm infections have an immunomodulatory effect by impairing the immune response to an exogenous antigen during infection. The hookworm-associated immunodepression may have important implications for design of clinical trials of human vaccines and vaccination strategies.
authors.affiliation: Department of Microbiology and Tropical Medicine, George Washington University Medical Center, Washington, DC 20037, USA.
authors.forename: Kashinath
authors.initials: K
authors.lastname: Ghosh
authors.forename: Wenhui
authors.initials: W
authors.lastname: Wu
authors.forename: Adrienne D
authors.initials: AD
authors.lastname: Antoine
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Bottazzi
authors.forename: Jesus G
authors.initials: JG
authors.lastname: Valenzuela
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Hotez
authors.forename: Susana
authors.initials: S
authors.lastname: Mendez
mesh_terms: D000276:Adjuvants, Immunologic; D000722:Ancylostoma / Q000145:classification / Q000276:immunology*; D000724:Ancylostomiasis / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control*; D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood*; D006224:Cricetinae; D015801:Helminth Proteins / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007114:Immunization; D008647:Mesocricetus; D062605:Quillaja Saponins; D011993:Recombinant Fusion Proteins / Q000276:immunology; D012503:Saponins; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology*
chemical_list: C483968:ASP-2 protein, Ancylostoma ceylanicum; D000276:Adjuvants, Immunologic; D000909:Antibodies, Helminth; D015801:Helminth Proteins; D062605:Quillaja Saponins; D011993:Recombinant Fusion Proteins; D012503:Saponins; D014614:Vaccines, Synthetic; C046386:Quil A