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Unique IL-13Rα2-based HIV-1 vaccine strategy to enhance mucosal immunity, CD8(+) T-cell avidity and protective immunity.

Ranasinghe, C., Trivedi, S., Stambas, J. and Jackson, R. J. 2013, Unique IL-13Rα2-based HIV-1 vaccine strategy to enhance mucosal immunity, CD8(+) T-cell avidity and protective immunity., Mucosal immunology, vol. 6, no. 6, pp. 1068-1080, doi: 10.1038/mi.2013.1.

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Title Unique IL-13Rα2-based HIV-1 vaccine strategy to enhance mucosal immunity, CD8(+) T-cell avidity and protective immunity.
Author(s) Ranasinghe, C.
Trivedi, S.
Stambas, J.ORCID iD for Stambas, J. orcid.org/0000-0002-5690-2551
Jackson, R. J.
Journal name Mucosal immunology
Volume number 6
Issue number 6
Start page 1068
End page 1080
Total pages 13
Publisher Nature Publishing Group
Place of publication London, England
Publication date 2013-11
ISSN 1933-0219
1935-3456
Summary 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.
Language eng
DOI 10.1038/mi.2013.1
Field of Research 110704 Cellular Immunology
Socio Economic Objective 920109 Infectious Diseases
HERDC Research category C1 Refereed article in a scholarly journal
Grant ID NHMRC 508902
Copyright notice ©2013, Nature Publishing Group
Persistent URL http://hdl.handle.net/10536/DRO/DU:30053440

Document type: Journal Article
Collection: School of Medicine
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Created: Thu, 04 Jul 2013, 13:44:55 EST by John Stambas

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