Ov‐ASP‐1, the Onchocerca volvulus homologue of the activation associated secreted protein family is immunostimulatory and can induce protective anti‐larval immunity

• Published in: Parasite immunology Vol. 26; no. 1; pp. 53 - 62
• Main Authors: MacDonald, A. J., Tawe, W., Leon, O., Cao, L., Liu, J., Oksov, Y., Abraham, D., Lustigman, S.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01-01-2004
• Subjects: adjuvant; Adjuvants, Immunologic; Aluminum Hydroxide - immunology; Animals; Antibodies, Helminth - blood; Antigens, Helminth - genetics; Antigens, Helminth - immunology; Antigens, Helminth - metabolism; Cell Culture Techniques; Esophagus - metabolism; Freund's Adjuvant; helminth; Helminth Proteins - genetics; Helminth Proteins - immunology; Helminth Proteins - metabolism; Humans; Immunoglobulin E - blood; Immunoglobulin G - blood; Interferon-gamma - analysis; Interferon-gamma - biosynthesis; Interleukin-5 - analysis; Interleukin-5 - biosynthesis; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; Mice; Mice, Inbred BALB C; Onchocerca volvulus; Onchocerca volvulus - immunology; Onchocerciasis - immunology; Onchocerciasis - parasitology; Onchocerciasis - prevention & control; Recombinant Proteins - immunology; Secretory Vesicles - metabolism; Th1; Th2; Vaccination; vaccine
• ISSN: 0141-9838; 1365-3024
• DOI: 10.1111/j.0141-9838.2004.00685.x

Summary
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.