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Remakus S , Ma X , Tang L , Xu RH , Knudson C , Melo-Silva CR , Rubio D , Kuo YM , Andrews A , Sigal LJ
Cutting Edge: Protection by Antiviral Memory CD8 T Cells Requires Rapidly Produced Antigen in Large Amounts
J Immunol. 2018 May 15;200(10) :3347-3352
PMID: 29643193    PMCID: PMC5940544    URL: https://www.ncbi.nlm.nih.gov/pubmed/29643193
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Numerous attempts to produce antiviral vaccines by harnessing memory CD8 T cells have failed. A barrier to progress is that we do not know what makes an Ag a viable target of protective CD8 T cell memory. We found that in mice susceptible to lethal mousepox (the mouse homolog of human smallpox), a dendritic cell vaccine that induced memory CD8 T cells fully protected mice when the infecting virus produced Ag in large quantities and with rapid kinetics. Protection did not occur when the Ag was produced in low amounts, even with rapid kinetics, and protection was only partial when the Ag was produced in large quantities but with slow kinetics. Hence, the amount and timing of Ag expression appear to be key determinants of memory CD8 T cell antiviral protective immunity. These findings may have important implications for vaccine design.
1550-6606 Remakus, Sanda Ma, Xueying Tang, Lingjuan Xu, Ren-Huan Knudson, Cory Melo-Silva, Carolina R Rubio, Daniel Kuo, Yin-Ming Andrews, Andrew ORCID: http://orcid.org/0000-0002-2529-3714 Sigal, Luis J ORCID: http://orcid.org/0000-0001-6642-5472 R01 AI065544/AI/NIAID NIH HHS/United States R01 AI110457/AI/NIAID NIH HHS/United States T32 CA009035/CA/NCI NIH HHS/United States U19 AI083008/AI/NIAID NIH HHS/United States Journal Article United States J Immunol. 2018 Apr 11. pii: jimmunol.1701568. doi: 10.4049/jimmunol.1701568.