AUTHOR=Beavis Ashley C. , Wee Edmund G. -T. , Akis Yildirim Belkis M. , Borthwick Nicola , He Biao , Hanke Tomáš 

TITLE=Combined intranasal and intramuscular parainfluenza 5-, simian adenovirus ChAdOx1- and poxvirus MVA-vectored vaccines induce synergistically HIV-1-specific T cells in the mucosa

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1186478

DOI=10.3389/fimmu.2023.1186478

ISSN=1664-3224

ABSTRACT=<sec><title>Introduction</title><p>The primary goal of this work is to broaden and enhance the options for induction of protective CD8<sup>+</sup> T cells against HIV-1 and respiratory pathogens.</p></sec><sec><title>Methods</title><p>We explored the advantages of the parainfluenza virus 5 (PIV5) vector for delivery of pathogen-derived transgenes alone and in combination with the in-human potent regimen of simian adenovirus ChAdOx1 prime-poxvirus MVA boost delivering bi-valent mosaic of HIV-1 conserved regions designated HIVconsvX.</p></sec><sec><title>Results</title><p>We showed in BALB/c mice that the PIV5 vector expressing the HIVconsvX immunogens could be readily incorporated with the other two vaccine modalities into a single regimen and that for specific vector combinations, mucosal CD8<sup>+</sup> T-cell induction was enhanced synergistically by a combination of the intranasal and intramuscular routes of administration.</p></sec><sec><title>Discussion</title><p>Encouraging safety and immunogenicity data from phase 1 human trials of ChAdOx1- and MVA-vectored vaccines for HIV-1, and PIV5-vectored vaccines for SARS-CoV-2 and respiratory syncytial virus pave the way for combining these vectors for HIV-1 and other indications in humans.</p></sec>