Unique IL-13Rα2-based HIV-1 vaccine strategy to enhance mucosal immunity, CD8(+) T-cell avidity and protective immunity.
Data(s) |
13/02/2013
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Resumo |
We have established that mucosal immunization can generate high-avidity human immunodeficiency virus (HIV)- specific CD8þ 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 a2 (IL-13Ra2), 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-13Ra2-adjuvanted vaccines have shown to induce (i) enhanced HIV-specific CD8þ Tcells 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 CD8þ T-cell responses, in the lung, genito-rectal nodes (GN), and Peyer’s patch (PP). Data revealed that intranasal delivery of these IL-13Ra2-adjuvanted HIV vaccines recruited large numbers of unique antigen-presenting cell subsets to the lung mucosae, ultimately promoting the induction of high-avidity CD8þ Tcells. 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. |
Identificador | |
Idioma(s) |
eng |
Publicador |
Nature Publishing Group |
Relação |
NHMRC 508902 http://dro.deakin.edu.au/eserv/DU:30053440/stambas-uniqueil-inpress-2013.pdf http://doi.org/10.1038/mi.2013.1 |
Direitos |
2013, Nature Publishing Group |
Tipo |
Journal Article |