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.