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Identification of poxvirus CD8+ T cell determinants to enable rational design and characterization of smallpox vaccines

Citation

Tscharke, DC and Karupiah, G and Zhou, J and Palmore, T and Irvine, KR and Mansour Haeryfar, SM and Williams, S and Sidney, J and Sette, A and Bennink, JR and Yewdell, JW, Identification of poxvirus CD8+ T cell determinants to enable rational design and characterization of smallpox vaccines, The Journal of Experimental Medicine, 201, (1) pp. 95-104. ISSN 0022-1007 (2005) [Refereed Article]


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Copyright Statement

Author copyright 2002

DOI: doi:10.1084/jem.20041912

Abstract

The large size of poxvirus genomes has stymied attempts to identify determinants recognized by CD8+ T cells and greatly impeded development of mouse smallpox vaccination models. Here, we use a vaccinia virus (VACV) expression library containing each of the predicted 258 open reading frames to identify five peptide determinants that account for approximately half of the VACV-specific CD8+ T cell response in C57BL/6 mice. We show that the primary immunodominance hierarchy is greatly affected by the route of VACV infection and the poxvirus strain used. Modified vaccinia virus ankara (MVA), a candidate replacement smallpox vaccine, failed to induce responses to two of the defined determinants. This could not be predicted by genomic comparison of viruses and is not due strictly to limited MVA replication in mice. Several determinants are immunogenic in cowpox and ectromelia (mousepox) virus infections, and immunization with the immunodominant determinant provided significant protection against lethal mousepox. These findings have important implications for understanding poxvirus immunity in animal models and bench-marking immune responses to poxvirus vaccines in humans.

Item Details

Item Type:Refereed Article
Keywords:Cytotoxic T lymphocytes; orthopoxvirus; CD8 T cell determinants; H-2b
Research Division:Biomedical and Clinical Sciences
Research Group:Immunology
Research Field:Cellular immunology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Prevention of human diseases and conditions
UTAS Author:Karupiah, G (Associate Professor Guna Karupiah)
ID Code:142825
Year Published:2005
Web of Science® Times Cited:240
Deposited By:Medicine
Deposited On:2021-02-12
Last Modified:2021-05-27
Downloads:0

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