A HIV-Tat/C4-binding protein chimera encoded by a DNA vaccine is highly immunogenic and contains acute EcoHIV infection in mice

Tomusange, K, Wijesundara, D, Gummow, J, Garrod, T, Li, Y, Gray, L, Churchill, M, Grubor-Bauk, B and Gowan, E 2016, 'A HIV-Tat/C4-binding protein chimera encoded by a DNA vaccine is highly immunogenic and contains acute EcoHIV infection in mice', Scientific Reports, vol. 6, 29131, pp. 1-10.


Document type: Journal Article
Collection: Journal Articles

Title A HIV-Tat/C4-binding protein chimera encoded by a DNA vaccine is highly immunogenic and contains acute EcoHIV infection in mice
Author(s) Tomusange, K
Wijesundara, D
Gummow, J
Garrod, T
Li, Y
Gray, L
Churchill, M
Grubor-Bauk, B
Gowan, E
Year 2016
Journal name Scientific Reports
Volume number 6
Article Number 29131
Start page 1
End page 10
Total pages 10
Publisher Nature
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.
Subject Virology
Keyword(s) HIV-1 Tat Protein
Immunodeficiency Virus Shiv89.6p
Cynomolgus Monkeys
Neutralizing Antibodies
C4b-Binding Protein
Protective Efficacy
Rhesus Macaques
Plasma Iga
In-Vivo
Mucosal
DOI - identifier 10.1038/srep29131
Copyright notice © 2016 This work is licensed under a Creative Commons Attribution 4.0 International License.
ISSN 2045-2322
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