title: Human cytotoxic T lymphocyte responses to live attenuated 17D yellow fever vaccine: identification of HLA-B35-restricted CTL epitopes on nonstructural proteins NS1, NS2b, NS3, and the structural protein E.
abstract: Yellow fever virus (YFV) is a re-emerging problem despite the existence of an effective live-attenuated vaccine. The induction of YFV-neutralizing antibodies undoubtedly contributes to vaccine efficacy, but T lymphocyte responses to YFV likely play a role in long-term efficacy. We studied the T lymphocyte responses to YFV in four vaccinees. Proliferation and cytolytic responses to YFV were demonstrated in all subjects. We isolated 13 YFV-specific CD8(+) CTL lines that recognized epitopes on the E, NS1, NS2b, and NS3 proteins; eight CTL lines were HLA-B35-restricted. YFV-specific T cell responses were detectable by IFN gamma ELISPOT assays 14 days postvaccination, with T cell frequencies sustained for up to 19 months. To our knowledge, this is the first report of human T lymphocyte responses following YFV vaccination. These results indicate that the live 17D YFV vaccine induced CD8(+) T cell responses directed against at least four different HLA-B35-restricted YFV epitopes.
authors.affiliation: Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, Massachusetts 01655, USA.
authors.forename: Mary Dawn T
authors.initials: MD
authors.lastname: Co
authors.forename: Masanori
authors.initials: M
authors.lastname: Terajima
authors.forename: John
authors.initials: J
authors.lastname: Cruz
authors.forename: Francis A
authors.initials: FA
authors.lastname: Ennis
authors.forename: Alan L
authors.initials: AL
authors.lastname: Rothman
mesh_terms: D000483:Alleles; D002460:Cell Line; D018984:Epitopes, T-Lymphocyte; D015797:HLA-B35 Antigen / Q000235:genetics*; D006801:Humans; D008213:Lymphocyte Activation; D020365:RNA Helicases; D012697:Serine Endopeptidases; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000276:immunology; D017361:Viral Nonstructural Proteins / Q000276:immunology*; D015678:Viral Structural Proteins / Q000276:immunology*; D022341:Yellow Fever Vaccine / Q000276:immunology*; D015005:Yellow fever virus / Q000276:immunology; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D018984:Epitopes, T-Lymphocyte; D015797:HLA-B35 Antigen; D020365:RNA Helicases; D012697:Serine Endopeptidases; D014613:Vaccines, Attenuated; D017361:Viral Nonstructural Proteins; D015678:Viral Structural Proteins; D022341:Yellow Fever Vaccine; C100315:NS1 protein, Flavivirus; C080102:NS2B protein, flavivirus; C060028:NS3 protein, flavivirus; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases