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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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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: | 237 |
| Deposited By: | Medicine |
| Deposited On: | 2021-02-12 |
| Last Modified: | 2021-02-23 |
| Downloads: | 0 |
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