Deakin University
Browse
ashley-geneticallystablepoliovirus-2020.pdf (4.93 MB)

Genetically stable poliovirus vectors activate dendritic cells and prime antitumor CD8 T cell immunity

Download (4.93 MB)
Version 3 2024-06-18, 19:16
Version 2 2024-06-06, 12:09
Version 1 2020-02-07, 13:37
journal contribution
posted on 2024-06-18, 19:16 authored by MM Mosaheb, EY Dobrikova, MC Brown, Y Yang, J Cable, H Okada, SK Nair, DD Bigner, DM Ashley, M Gromeier
Viruses naturally engage innate immunity, induce antigen presentation, and mediate CD8 T cell priming against foreign antigens. Polioviruses can provide a context optimal for generating antigen-specific CD8 T cells, as they have natural tropism for dendritic cells, preeminent inducers of CD8 T cell immunity; elicit Th1-promoting inflammation; and lack interference with innate or adaptive immunity. However, notorious genetic instability and underlying neuropathogenicity has hampered poliovirus-based vector applications. Here we devised a strategy based on the polio:rhinovirus chimera PVSRIPO, devoid of viral neuropathogenicity after intracerebral inoculation in human subjects, for stable expression of exogenous antigens. PVSRIPO vectors infect, activate, and induce epitope presentation in DCs in vitro; they recruit and activate DCs with Th1-dominant cytokine profiles at the injection site in vivo. They efficiently prime tumor antigen-specific CD8 T cells in vivo, induce CD8 T cell migration to the tumor site, delay tumor growth and enhance survival in murine tumor models.

History

Journal

Nature Communications

Volume

11

Article number

524

Pagination

1-15

Location

Berlin, Germany

Open access

  • Yes

eISSN

2041-1723

Language

eng

Publication classification

C1 Refereed article in a scholarly journal

Copyright notice

2020, The Author(s)

Issue

1

Publisher

Nature Research

Usage metrics

    Research Publications

    Categories

    No categories selected

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC