Recombinant influenza virus expressing HIV-1 p24 capsid protein induces mucosal HIV-specific CD8 T-cell responses

Tan, Hyon-Xhi, Gilbertson, Brad P., Jegaskanda, Sinthujan, Alcantara, Seilajen, Amarasena, Thakshila, Stambas, John, McAuley, Julie L., Kent, Stephen J. and De Rose, Robert 2016, Recombinant influenza virus expressing HIV-1 p24 capsid protein induces mucosal HIV-specific CD8 T-cell responses, Vaccine, vol. 34, no. 9, pp. 1172-1179, doi: 10.1016/j.vaccine.2016.01.030.

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Title Recombinant influenza virus expressing HIV-1 p24 capsid protein induces mucosal HIV-specific CD8 T-cell responses
Author(s) Tan, Hyon-Xhi
Gilbertson, Brad P.
Jegaskanda, Sinthujan
Alcantara, Seilajen
Amarasena, Thakshila
Stambas, JohnORCID iD for Stambas, John
McAuley, Julie L.
Kent, Stephen J.
De Rose, Robert
Journal name Vaccine
Volume number 34
Issue number 9
Start page 1172
End page 1179
Total pages 8
Publisher Elsevier
Place of publication Amsterdam, The Netherlands
Publication date 2016-02-24
ISSN 0264-410X
Keyword(s) CD8 T-cell
Mucosal immunity
Science & Technology
Life Sciences & Biomedicine
Medicine, Research & Experimental
Research & Experimental Medicine
Summary Influenza viruses are promising mucosal vaccine vectors for HIV but their use has been limited by difficulties in engineering the expression of large amounts of foreign protein. We developed recombinant influenza viruses incorporating the HIV-1 p24 gag capsid into the NS-segment of PR8 (H1N1) and X31 (H3N2) influenza viruses with the use of multiple 2A ribosomal skip sequences. Despite the insertion of a sizable HIV-1 gene into the influenza genome, recombinant viruses were readily rescued to high titers. Intracellular expression of p24 capsid was confirmed by in vitro infection assays. The recombinant influenza viruses were subsequently tested as mucosal vaccines in BALB/c mice. Recombinant viruses were attenuated and safe in immunized mice. Systemic and mucosal HIV-specific CD8 T-cell responses were elicited in mice that were immunized via intranasal route with a prime-boost regimen. Isolated HIV-specific CD8 T-cells displayed polyfunctional cytokine and degranulation profiles. Mice boosted via intravaginal route induced recall responses from the distal lung mucosa and developed heightened HIV-specific CD8 T-cell responses in the vaginal mucosa. These findings demonstrate the potential utility of recombinant influenza viruses as vaccines for mucosal immunity against HIV-1 infection.
Language eng
DOI 10.1016/j.vaccine.2016.01.030
Field of Research 110309 Infectious Diseases
Socio Economic Objective 920109 Infectious Diseases
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2016, Elsevier
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Document type: Journal Article
Collections: Faculty of Health
School of Medicine
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