title: 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.
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 T(H) 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.
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA. alex@liai.org
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sette
authors.forename: Howard
authors.initials: H
authors.lastname: Grey
authors.forename: Carla
authors.initials: C
authors.lastname: Oseroff
authors.forename: Bjoern
authors.initials: B
authors.lastname: Peters
authors.forename: Magdalini
authors.initials: M
authors.lastname: Moutaftsi
authors.forename: Shane
authors.initials: S
authors.lastname: Crotty
authors.forename: Erika
authors.initials: E
authors.lastname: Assarsson
authors.forename: Jay
authors.initials: J
authors.lastname: Greenbaum
authors.forename: Yohan
authors.initials: Y
authors.lastname: Kim
authors.forename: Ravi
authors.initials: R
authors.lastname: Kolla
authors.forename: David
authors.initials: D
authors.lastname: Tscharke
authors.forename: David
authors.initials: D
authors.lastname: Koelle
authors.forename: R Paul
authors.initials: RP
authors.lastname: Johnson
authors.forename: Janice
authors.initials: J
authors.lastname: Blum
authors.forename: Steven
authors.initials: S
authors.lastname: Head
authors.forename: John
authors.initials: J
authors.lastname: Sidney
mesh_terms: D000818:Animals; D000917:Antibody Formation; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D017124:Conserved Sequence; D056738:Cross Protection; D016056:Immunodominant Epitopes / Q000276:immunology*; D008253:Macaca mulatta; D051379:Mice; D014615:Vaccinia / Q000276:immunology* / Q000821:virology; D014616:Vaccinia virus / Q000235:genetics* / Q000276:immunology; D012901:Variola virus / Q000235:genetics* / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D016056:Immunodominant Epitopes