Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/104020
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Type: Journal article
Title: Mucosal vaccination with a live recombinant rhinovirus followed by intradermal DNA administration elicits potent and protective HIV-specific immune responses
Author: Tomusange, K.
Wijesundara, D.
Gummow, J.
Wesselingh, S.
Suhrbier, A.
Gowans, E.
Grubor-Bauk, B.
Citation: Scientific Reports, 2016; 6(1):36658 -1-36658-11
Publisher: Nature Publishing Group
Issue Date: 2016
ISSN: 2045-2322
2045-2322
Statement of
Responsibility: 
Khamis Tomusange, Danushka Wijesundara, Jason Gummow, Steve Wesselingh, Andreas Suhrbier, Eric J. Gowans, Branka Grubor-Bauk
Abstract: Mucosal immunity is deemed crucial to control sexual transmission of human immunodeficiency virus (HIV). Herein we report the efficacy of a mucosal HIV vaccine strategy comprising intranasal (IN) vaccination with a cocktail of live recombinant human rhinoviruses (HRVs) encoding overlapping fragments of HIV Gag and full length Tat (rHRV-Gag/Tat) followed by intradermal (ID) vaccination with DNA vaccines encoding HIV Gag and Tat (pVAX-Gag-Tat). This heterologous prime-boost strategy will be referred to hereafter as rHRV-DNA. As a control, IN vaccination with wild type (wt)-HRV-A1 followed by a single ID dose of pVAX (wt-HRV-A1/pVAX vaccination) was included. rHRV-DNA vaccination elicited superior multi-functional CD8(+)T cell responses in lymphocytes harvested from mesenteric lymph nodes and spleens, and higher titres of Tat-specific antibodies in blood and vaginal lavages, and reduced the viral load more effectively after challenge with EcoHIV, a murine HIV challenge model, in peritoneal macrophages, splenocytes and blood compared compared with wt-HRV-A1/pVAX vaccination or administration of 3 ID doses of pVAX-Gag-Tat (3X pVAX-Gag-Tat vaccination). These data provide the first evidence that a rHRV-DNA vaccination regimen can induce HIV-specific immune responses in the gut, vaginal mucosa and systemically, and supports further testing of this regimen in the development of an effective mucosally-targeted HIV-1 vaccine.
Keywords: CD8-Positive T-Lymphocytes
Animals
Mice, Inbred BALB C
Humans
Mice
Rhinovirus
HIV-1
HIV Infections
Vaccines, DNA
AIDS Vaccines
Immunity, Cellular
Female
gag Gene Products, Human Immunodeficiency Virus
tat Gene Products, Human Immunodeficiency Virus
Description: Published: 17 November 2016
Rights: © The Author(s) 2016. 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/
DOI: 10.1038/srep36658
Grant ID: http://purl.org/au-research/grants/nhmrc/1026293
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