Unique IL-13Rα2-based HIV-1 vaccine strategy to enhance mucosal immunity, CD8+ T-cell avidity and protective immunity
| Autor: | Ronald J. Jackson, Charani Ranasinghe, John Stambas, Shubhanshi Trivedi |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Cytotoxicity
Immunologic Cellular immunity Immunology HIV Core Protein p24 HIV Infections chemical and pharmacologic phenomena CD8-Positive T-Lymphocytes Biology Lymphocyte Activation Protein Engineering Mice Immunity Animals Humans Immunology and Allergy Cytotoxic T cell Avidity Antigen-presenting cell Immunity Mucosal Lung Cells Cultured AIDS Vaccines Mice Knockout Mice Inbred BALB C Interleukin-13 Receptors Interleukin-13 Interleukin-13 Receptor alpha1 Subunit Virology Vaccination Immunization Interleukin 13 HIV-1 Female Mutant Proteins |
| Zdroj: | Mucosal Immunology. 6:1068-1080 |
| ISSN: | 1933-0219 |
| DOI: | 10.1038/mi.2013.1 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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