Persistent Zika Virus Clinical Susceptibility despite Reduced Viral Burden in Mice with Expanded Virus-Specific CD8 + T Cells Primed by Recombinant Listeria monocytogenes

Vaccines against Zika virus (ZIKV) infection that target CD8 T cells are of considerable interest because Abs may enhance infection susceptibility. However, whether CD8 T cells are protective or promote susceptibility to clinical infection symptoms remains uncertain. To more precisely investigate ZI...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2020-07, Vol.205 (2), p.447-453
Main Authors: Burg, Ashley R, Erickson, John J, Turner, Lucien H, Pham, Giang, Kinder, Jeremy M, Way, Sing Sing
Format: Article
Language:English
Subjects:
Animals
Antibodies, Blocking - administration & dosage
CD8-Positive T-Lymphocytes - immunology
Cells, Cultured
Disease Resistance
Disease Susceptibility
Humans
Listeria monocytogenes - physiology
Listeriosis - immunology
Mice
Mice, Inbred C57BL
Mice, Knockout
Peptides - immunology
Receptor, Interferon alpha-beta - genetics
Receptor, Interferon alpha-beta - metabolism
Viral Envelope Proteins - immunology
Viral Load
Zika Virus - physiology
Zika Virus Infection - immunology
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Summary:Vaccines against Zika virus (ZIKV) infection that target CD8 T cells are of considerable interest because Abs may enhance infection susceptibility. However, whether CD8 T cells are protective or promote susceptibility to clinical infection symptoms remains uncertain. To more precisely investigate ZIKV-specific CD8 T cells in isolation, we engineered a -based vector to express a single MHC class I-restricted immune dominant peptide, E294-302, from ZIKV envelope protein. We show accumulation of activated ZIKV-specific CD8 T cells primed by recombinant is associated with reductions in circulating virus levels after ZIKV challenge in type I IFN receptor-deficient mice and wildtype mice administered neutralizing Abs against type I IFN receptor. Interestingly, susceptibility to ZIKV clinical infection including weight loss and mortality each persists and is neither significantly improved nor worsened compared with isogenic -primed control mice. These data demonstrating persistent ZIKV clinical susceptibility despite reduced viral burden in mice with expanded virus-specific CD8 T cells highlights the need for targeting other adaptive immune components in developing vaccines against ZIKV infection.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.1901412