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Structural and functional characterisation of the Toll like receptor 9 of Aotus nancymaae , a non-human primate model for malaria vaccine development

Spirig, Rolf ; Peduzzi, Elisabetta ; Patarroyo, Manuel ; Pluschke, Gerd ; Daubenberger, Claudia

In: Immunogenetics, 2005, vol. 57, no. 3-4, p. 283-288

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    Titre
    • Structural and functional characterisation of the Toll like receptor 9 of Aotus nancymaae , a non-human primate model for malaria vaccine development
    Auteur
    • Spirig, Rolf. Department of Medical Parasitology and Biology of Infection, Molecular Immunology, Swiss Tropical Institute, Socinstrasse 57, 4002, Basel, Switzerland
    • Peduzzi, Elisabetta. Department of Medical Parasitology and Biology of Infection, Molecular Immunology, Swiss Tropical Institute, Socinstrasse 57, 4002, Basel, Switzerland
    • Patarroyo, Manuel. Fundación Instituto de Inmunología de Colombia, FIDIC, Calle 26 No 50-00, Santa Fe de Bogotá, Bogota, Colombia
    • Pluschke, Gerd. Department of Medical Parasitology and Biology of Infection, Molecular Immunology, Swiss Tropical Institute, Socinstrasse 57, 4002, Basel, Switzerland
    • Daubenberger, Claudia. Department of Medical Parasitology and Biology of Infection, Molecular Immunology, Swiss Tropical Institute, Socinstrasse 57, 4002, Basel, Switzerland
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Immunogenetics, 2005, vol. 57, no. 3-4, p. 283-288. Springer-Verlag; http://www.springer.de
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:312677
    Summary
    In the absence of suitable rodent animal models for Plasmodium falciparum malaria, the efficacy testing of asexual blood-stage vaccine candidates in Aotus nancymaae represents a tool to select between different formulations before conducting expensive human clinical trials. CpG oligonucleotides (ODN) specifically promote the production of pro-inflammatory and Th1-type cytokines and they enhance the immunogenicity of co-administered antigens. Toll like receptor 9 (TLR-9) binds directly and sequence-specifically to single-stranded un-methylated CpG-DNA mediating the biological effects of CpG ODN. We cloned and functionally characterised the TLR-9 cDNA of A. nancymaae. The cDNA encompassed 3,099bp predicted to code for 1,032 amino acid residues. Results of homology searches to human TLR-9 suggested that the receptor is 93 and 94% identical at the nucleotide and amino acid sequence levels, respectively. Stimulation of splenocytes of A. nancymaae with CpG ODN resulted in proliferative responses in all animals analysed. FACS analysis of cultures incubated with CpG ODN 2006 indicated that the B cell marker CD20 was up-regulated consistent with B cell activation. The high level of sequence conservation of Aona-TLR-9 reinforces the suitability of A. nancymaae as animal model for malaria subunit vaccine development