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

• Published in: Frontiers in immunology 2023-07, Vol.14, p.1186478-1186478
• Main Authors: Beavis, Ashley C, Wee, Edmund G-T, Akis Yildirim, Belkis M, Borthwick, Nicola, He, Biao, Hanke, Tomáš
• Format: Article
• Language: English
• Subjects: CD8+ T cells; ChAdOx1; HIV vaccine; Immunology; MVA; PIV5
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2023.1186478

The primary goal of this work is to broaden and enhance the options for induction of protective CD8 T cells against HIV-1 and respiratory pathogens. 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. 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 T-cell induction was enhanced synergistically by a combination of the intranasal and intramuscular routes of administration. 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.