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Recombinant influenza virus expressing HIV-1 p24 capsid protein induces mucosal HIV-specific CD8 T-cell responses
journal contribution
posted on 2016-02-24, 00:00 authored by H-X Tan, B P Gilbertson, S Jegaskanda, S Alcantara, T Amarasena, John StambasJohn Stambas, J L McAuley, S J Kent, R De RoseInfluenza 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.
History
Journal
VaccineVolume
34Issue
9Pagination
1172 - 1179Publisher
ElsevierLocation
Amsterdam, The NetherlandsPublisher DOI
ISSN
0264-410XeISSN
1873-2518Language
engPublication classification
C Journal article; C1 Refereed article in a scholarly journalCopyright notice
2016, ElsevierUsage metrics
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