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

Virology. 2002 Feb 1;293(1):151-63. doi: 10.1006/viro.2001.1255.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Cell Line
  • Epitopes, T-Lymphocyte*
  • HLA-B35 Antigen / genetics*
  • Humans
  • Lymphocyte Activation
  • RNA Helicases
  • Serine Endopeptidases
  • T-Lymphocytes, Cytotoxic / immunology*
  • Vaccines, Attenuated / immunology
  • Viral Nonstructural Proteins / immunology*
  • Viral Structural Proteins / immunology*
  • Yellow Fever Vaccine / immunology*
  • Yellow fever virus / immunology

Substances

  • Epitopes, T-Lymphocyte
  • HLA-B35 Antigen
  • NS1 protein, Flavivirus
  • NS2B protein, flavivirus
  • NS3 protein, flavivirus
  • Vaccines, Attenuated
  • Viral Nonstructural Proteins
  • Viral Structural Proteins
  • Yellow Fever Vaccine
  • Serine Endopeptidases
  • RNA Helicases