title: Differences between T cell epitopes recognized after immunization and after infection.
abstract: Evidence suggests that cellular immune responses play a crucial role in the control of HIV and SIV replication in infected individuals. Several vaccine strategies have therefore targeted these CD8(+) and CD4(+) responses. Whether vaccination induces the same repertoire of responses seen after infection is, however, a key unanswered question in HIV vaccine development. We therefore compared the epitope specificity induced by vaccination to that present postchallenge in the peripheral blood. Intracellular cytokine staining of PBMC stimulated with overlapping 15/20-mer peptides spanning the proteins of SIV were measured after DNA/modified vaccinia Ankara vaccination of eight rhesus macaques. Lymphocytes from 8 animals recognized a total of 39 CD8 epitopes and 41 CD4 epitopes encoded by the vaccine. T cell responses were again monitored after challenge with SIVmac239 to investigate the evolution of these responses. Only 57% of all CD8(+) T cell responses and 19% of all CD4(+) T cell responses present after vaccination were recalled after infection as measured in the peripheral blood. Interestingly, 29 new CD8 epitopes and 5 new CD4 epitopes were recognized by PBMC in the acute phase. These new epitopes were not detected after vaccination, and only some of them were maintained in the chronic phase (33% of CD8 and no CD4 responses). Additionally, 24 new CD8 epitopes and 7 new CD4 epitopes were recognized by PBMC in the chronic phase of infection. The repertoire of the immune response detected in the peripheral blood after immunization substantially differed from the immune response detected in the peripheral blood after infection.
authors.affiliation: Wisconsin National Primate Research Center, University of Wisconsin, 1220 Capital Court, Madison, WI 53715, USA.
authors.forename: Thorsten U
authors.initials: TU
authors.lastname: Vogel
authors.forename: Helen
authors.initials: H
authors.lastname: Horton
authors.forename: Deborah H
authors.initials: DH
authors.lastname: Fuller
authors.forename: Donald K
authors.initials: DK
authors.lastname: Carter
authors.forename: Kathy
authors.initials: K
authors.lastname: Vielhuber
authors.forename: David H
authors.initials: DH
authors.lastname: O'Connor
authors.forename: Tim
authors.initials: T
authors.lastname: Shipley
authors.forename: Jim
authors.initials: J
authors.lastname: Fuller
authors.forename: Gerd
authors.initials: G
authors.lastname: Sutter
authors.forename: Volker
authors.initials: V
authors.lastname: Erfle
authors.forename: Nancy
authors.initials: N
authors.lastname: Wilson
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Picker
authors.forename: David I
authors.initials: DI
authors.lastname: Watkins
mesh_terms: D000285:Administration, Rectal; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D002461:Cell Line, Transformed; D018984:Epitopes, T-Lymphocyte / Q000032:analysis* / Q000235:genetics / Q000276:immunology*; D007111:Immunity, Cellular / Q000235:genetics; D007117:Immunization, Secondary; D007271:Injections, Intradermal; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000821:virology; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000032:analysis / Q000235:genetics / Q000276:immunology; D010449:Peptide Mapping; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*; D014764:Viral Proteins / Q000032:analysis / Q000235:genetics / Q000276:immunology
chemical_list: D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments; D018449:SAIDS Vaccines; D014614:Vaccines, Synthetic; D014764:Viral Proteins