University Of Tasmania
36. Tscharke et al.pdf (468.88 kB)
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Identification of poxvirus CD8+ T cell determinants to enable rational design and characterization of smallpox vaccines

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journal contribution
posted on 2023-05-20, 21:01 authored by Tscharke, DC, Gunasegaran KarupiahGunasegaran Karupiah, Zhou, J, Palmore, T, Irvine, KR, Mansour Haeryfar, SM, Williams, S, Sidney, J, Sette, A, Bennink, JR, Yewdell, JW
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.


Publication title

The Journal of Experimental Medicine








Tasmanian School of Medicine


Rockefeller Univ Press

Place of publication

1114 First Ave, 4Th Fl, New York, USA, Ny, 10021

Rights statement

Author copyright 2002

Repository Status

  • Open

Socio-economic Objectives

Prevention of human diseases and conditions; Treatment of human diseases and conditions