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

Mosaheb, MM, Dobrikova, EY, Brown, MC, Yang, Y, Cable, J, Okada, H, Nair, SK, Bigner, DD, Ashley, DM and Gromeier, M 2020, Genetically stable poliovirus vectors activate dendritic cells and prime antitumor CD8 T cell immunity, Nature Communications, vol. 11, no. 1, pp. 1-15, doi: 10.1038/s41467-019-13939-z.

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Title Genetically stable poliovirus vectors activate dendritic cells and prime antitumor CD8 T cell immunity
Author(s) Mosaheb, MM
Dobrikova, EY
Brown, MC
Yang, Y
Cable, J
Okada, H
Nair, SK
Bigner, DD
Ashley, DM
Gromeier, M
Journal name Nature Communications
Volume number 11
Issue number 1
Article ID 524
Start page 1
End page 15
Total pages 15
Publisher Nature Research
Place of publication Berlin, Germany
Publication date 2020-01-27
ISSN 2041-1723
Keyword(s) Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
TRANSLATION INITIATION
EXPRESSION VECTORS
I INTERFERON
RNA
VACCINE
BINDING
TOLERANCE
SITE
NEUROVIRULENCE
PROLIFERATION
Summary 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.
Language eng
DOI 10.1038/s41467-019-13939-z
Indigenous content off
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2020, The Author(s)
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30134756

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
Open Access Collection
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.