title: Unique IL-13Rα2-based HIV-1 vaccine strategy to enhance mucosal immunity, CD8(+) T-cell avidity and protective immunity.
abstract: We have established that mucosal immunization can generate high-avidity human immunodeficiency virus (HIV)-specific CD8(+) T cells compared with systemic immunization, and interleukin (IL)-13 is detrimental to the functional avidity of these T cells. We have now constructed two unique recombinant HIV-1 vaccines that co-express soluble or membrane-bound forms of the IL-13 receptor α2 (IL-13Rα2), which can "transiently" block IL-13 activity at the vaccination site causing wild-type animals to behave similar to an IL-13 KO animal. Following intranasal/intramuscular prime-boost immunization, these IL-13Rα2-adjuvanted vaccines have shown to induce (i) enhanced HIV-specific CD8(+) T cells with higher functional avidity, with broader cytokine/chemokine profiles and greater protective immunity using a surrogate mucosal HIV-1 challenge, and also (ii) excellent multifunctional mucosal CD8(+) T-cell responses, in the lung, genito-rectal nodes (GN), and Peyer's patch (PP). Data revealed that intranasal delivery of these IL-13Rα2-adjuvanted HIV vaccines recruited large numbers of unique antigen-presenting cell subsets to the lung mucosae, ultimately promoting the induction of high-avidity CD8(+) T cells. We believe our novel IL-13R cytokine trap vaccine strategy offers great promise for not only HIV-1, but also as a platform technology against range of chronic infections that require strong sustained high-avidity mucosal/systemic immunity for protection.
authors: Molecular Mucosal Vaccine Immunology Group, Department of Immunology, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia.
authors: C
authors: C
authors: Ranasinghe
authors: S
authors: S
authors: Trivedi
authors: J
authors: J
authors: Stambas
authors: R J
authors: RJ
authors: Jackson
mesh_terms: D016915:AIDS Vaccines; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D005260:Female; D016655:HIV Core Protein p24 / Q000235:genetics / Q000378:metabolism*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D018928:Immunity, Mucosal; D018793:Interleukin-13 / Q000235:genetics / Q000378:metabolism*; D053661:Interleukin-13 Receptor alpha1 Subunit; D008168:Lung / Q000276:immunology* / Q000821:virology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D050505:Mutant Proteins / Q000235:genetics; D015202:Protein Engineering; D053660:Receptors, Interleukin-13 / Q000235:genetics / Q000378:metabolism*
chemical_list: D016915:AIDS Vaccines; D016655:HIV Core Protein p24; C508181:IL13RA1 protein, human; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D050505:Mutant Proteins; D053660:Receptors, Interleukin-13