Ov-ASP-1, the Onchocerca volvulus homologue of the activation associated secreted protein family is immunostimulatory and can induce protective anti-larval immunity
Corresponding Author
A. J. MacDonald
Laboratory of Molecular Parasitology and
Angus J. MacDonald, PhD, Molecular Parasitology Laboratory, Lindsley F. Kimball Research Institute, The New York Blood Center, 310 East 67th Street, New York, NY 10021, USA (e-mail: [email protected]).Search for more papers by this authorO. Leon
Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA, USA
Search for more papers by this authorY. Oksov
Electron Microscopy Laboratory, Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA,
Search for more papers by this authorD. Abraham
Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA, USA
Search for more papers by this authorCorresponding Author
A. J. MacDonald
Laboratory of Molecular Parasitology and
Angus J. MacDonald, PhD, Molecular Parasitology Laboratory, Lindsley F. Kimball Research Institute, The New York Blood Center, 310 East 67th Street, New York, NY 10021, USA (e-mail: [email protected]).Search for more papers by this authorO. Leon
Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA, USA
Search for more papers by this authorY. Oksov
Electron Microscopy Laboratory, Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA,
Search for more papers by this authorD. Abraham
Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA, USA
Search for more papers by this authorSummary
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-γ 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.
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