Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/101851
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Type: Journal article
Title: A HIV-Tat/C4-binding protein chimera encoded by a DNA vaccine is highly immunogenic and contains acute EcoHIV infection in mice
Author: Tomusange, K.
Wijesundara, D.
Gummow, J.
Garrod, T.
Li, Y.
Gray, L.
Churchill, M.
Grubor-Bauk, B.
Gowans, E.
Citation: Scientific Reports, 2016; 6(1):29131-1-29131-10
Publisher: Nature Publishing Group
Issue Date: 2016
ISSN: 2045-2322
2045-2322
Statement of
Responsibility: 
Khamis Tomusange, Danushka Wijesundara, Jason Gummow, Tamsin Garrod, Yanrui Li, Lachlan Gray, Melissa Churchill, Branka Grubor-Bauk and Eric J. Gowans
Abstract: DNA vaccines are cost-effective to manufacture on a global scale and Tat-based DNA vaccines have yielded protective outcomes in preclinical and clinical models of human immunodeficiency virus (HIV), highlighting the potential of such vaccines. However, Tat-based DNA vaccines have been poorly immunogenic, and despite the administration of multiple doses and/or the addition of adjuvants, these vaccines are not in general use. In this study, we improved Tat immunogenicity by fusing it with the oligomerisation domain of a chimeric C4-binding protein (C4b-p), termed IMX313, resulting in Tat heptamerisation and linked Tat to the leader sequence of tissue plasminogen activator (TPA) to ensure that the bulk of heptamerised Tat is secreted. Mice vaccinated with secreted Tat fused to IMX313 (pVAX-sTat-IMX313) developed higher titres of Tat-specific serum IgG, mucosal sIgA and cell-mediated immune (CMI) responses, and showed superior control of EcoHIV infection, a surrogate murine HIV challenge model, compared with animals vaccinated with other test vaccines. Given the crucial contribution of Tat to HIV-1 pathogenesis and the precedent of Tat-based DNA vaccines in conferring some level of protection in animal models, we believe that the virologic control demonstrated with this novel multimerised Tat vaccine highlights the promise of this vaccine candidate for humans.
Keywords: Animals; Chimera; Humans; Mice; HIV-1; HIV Infections; Recombinant Fusion Proteins; Vaccines, DNA; HIV Antibodies; Immunity, Cellular; Apoptosis Regulatory Proteins; tat Gene Products, Human Immunodeficiency Virus; Survivin
Rights: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
RMID: 0030050144
DOI: 10.1038/srep29131
Grant ID: http://purl.org/au-research/grants/nhmrc/1026293
Appears in Collections:Medicine publications

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