title: Ov-ASP-1, the Onchocerca volvulus homologue of the activation associated secreted protein family is immunostimulatory and can induce protective anti-larval immunity.
abstract: Vaccination of mice with a recombinant protein, Ov-ASP-1, the Onchocerca volvulus homologue of the activation associated secreted gene family stimulated very high titres of both IgG1 and IgG2a without adjuvant. rOv-ASP-1 was also immuno-reactive with IgG isotypes from both O. volvulus-infected (INF) and putatively immune (PI) humans, with higher IgG4 in the former group. The protein also stimulated IFN-gamma secretion by PBMC from INF and PI and IL-5 only in INF. Using a mouse diffusion chamber model, vaccination with rOv-ASP-1 resulted in partial but significant protection against challenge with infective third-stage larvae (L3) but only when formulated with Freund's complete adjuvant (FCA) or alum. Protection was Th1-dependent (highly elevated IgG2a) with FCA and contingent on a strongly Th2-skewed (IgG1) response with alum. IgE responses to rOv-ASP-1 with or without adjuvant were weak or absent. When immunization using rOv-ASP-1 in adjuvant failed to induce adequate Th1 (FCA) or Th2 (alum) responses, protection efficacy was compromised. The recombinant protein appears to stimulate a mixed Th1/Th2 response but the outcome in terms of protective immunity is the result of a subtle interplay of its intrinsic and adjuvant-augmented properties. Ov-ASP-1 is potentially secreted based on its localization in the secretory granules of L3.
authors.affiliation: Laboratory of Molecular Parasitology, Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10021, USA. amacdonald@nybloodcentre.org
authors.forename: A J
authors.initials: AJ
authors.lastname: MacDonald
authors.forename: W
authors.initials: W
authors.lastname: Tawe
authors.forename: O
authors.initials: O
authors.lastname: Leon
authors.forename: L
authors.initials: L
authors.lastname: Cao
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: Y
authors.initials: Y
authors.lastname: Oksov
authors.forename: D
authors.initials: D
authors.lastname: Abraham
authors.forename: S
authors.initials: S
authors.lastname: Lustigman
mesh_terms: D000276:Adjuvants, Immunologic; D000536:Aluminum Hydroxide / Q000276:immunology; D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood; D000947:Antigens, Helminth / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018929:Cell Culture Techniques; D004947:Esophagus / Q000378:metabolism; D005620:Freund's Adjuvant; D015801:Helminth Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000032:analysis / Q000096:biosynthesis; D015848:Interleukin-5 / Q000032:analysis / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D017181:Onchocerca volvulus / Q000276:immunology*; D009855:Onchocerciasis / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control*; D011994:Recombinant Proteins / Q000276:immunology; D022142:Secretory Vesicles / Q000378:metabolism; D014611:Vaccination
chemical_list: D000276:Adjuvants, Immunologic; D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D015801:Helminth Proteins; D007074:Immunoglobulin G; D015848:Interleukin-5; C414408:Ov-ASP-1 protein, Onchocerca volvulus; D011994:Recombinant Proteins; D007073:Immunoglobulin E; D000536:Aluminum Hydroxide; D007371:Interferon-gamma; D005620:Freund's Adjuvant