Definition of epitopes and antigens recognized by vaccinia specific immune responses: Their conservation in variola virus sequences, and use as a model system to study complex pathogens

Alessandro Sette, Howard Grey, Carla Oseroff, Bjoern Peters, Magdalini Moutaftsi, Shane Crotty, Erika Assarsson, Jay Greenbaum, Yohan Kim, Ravi Kolla, David Tscharke, David Koelle, R. Paul Johnson, Janice Blum, Steven Head, John Sidney

Research output: Contribution to journalReview article

30 Scopus citations

Abstract

In the last few years, a wealth of information has become available relating to the targets of vaccinia virus (VACV)-specific CD4+ T cell, CD8+ T cell and antibody responses. Due to the large size of its genome, encoding more than 200 different proteins, VACV represents a useful model system to study immunity to complex pathogens. Our data demonstrate that both cellular and humoral responses target a large number of antigens and epitopes. This broad spectrum of targets is detected in both mice and humans. CD4+ T cell responses target late and structural antigens, while CD8+ T cells preferentially recognize early antigens. While both CD4+ and CD8+ T cell responses target different types of antigens, the antigens recognized by TH cells are highly correlated with those recognized by antibody responses. We further show that protein abundance and antibody recognition can be used to predict antigens recognized by CD4+ T cell responses, while early expression at the mRNA level predicts antigens targeted by CD8+ T cells. Finally, we find that the vast majority of VACV epitopes are conserved in variola virus (VARV), thus suggesting that the epitopes defined herein also have relevance for the efficacy of VACV as a smallpox vaccine.

Original languageEnglish (US)
Pages (from-to)G21-G26
JournalVaccine
Volume27
Issue numberSUPPL.6
DOIs
StatePublished - Dec 30 2009

Keywords

  • Epitope
  • Smallpox
  • Vaccinia

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)
  • Molecular Medicine

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    Sette, A., Grey, H., Oseroff, C., Peters, B., Moutaftsi, M., Crotty, S., Assarsson, E., Greenbaum, J., Kim, Y., Kolla, R., Tscharke, D., Koelle, D., Johnson, R. P., Blum, J., Head, S., & Sidney, J. (2009). Definition of epitopes and antigens recognized by vaccinia specific immune responses: Their conservation in variola virus sequences, and use as a model system to study complex pathogens. Vaccine, 27(SUPPL.6), G21-G26. https://doi.org/10.1016/j.vaccine.2009.10.011