title: A Single 17D Yellow Fever Vaccination Provides Lifelong Immunity; Characterization of Yellow-Fever-Specific Neutralizing Antibody and T-Cell Responses after Vaccination.
abstract: BACKGROUND
  Prompted by recent amendments of Yellow Fever (YF) vaccination guidelines from boost to single vaccination strategy and the paucity of clinical data to support this adjustment, we used the profile of the YF-specific CD8+ T-cell subset profiles after primary vaccination and neutralizing antibodies as a proxy for potentially longer lasting immunity.
  
  
  RESULTS
  PBMCs and serum were collected in six individuals on days 0, 3, 5, 12, 28 and 180, and in 99 individuals >10 years after YF-vaccination. Phenotypic characteristics of YF- tetramer+ CD8+ T-cells were determined using class I tetramers. Antibody responses were measured using a standardized plaque reduction neutralization test (PRNT). Also, characteristics of YF-tetramer positive CD8+ T-cells were compared between individuals who had received a primary- and a booster vaccination. YF-tetramer+ CD8+ T-cells were detectable on day 12 (median tetramer+ cells as percentage of CD8+ T-cells 0.2%, range 0.07-3.1%). On day 180, these cells were still present (median 0.06%, range 0.02-0.78%). The phenotype of YF-tetramer positive CD8+ T-cells shifted from acute phase effector cells on day 12, to late differentiated or effector memory phenotype (CD45RA-/+CD27-) on day 28. Two subsets of YF-tetramer positive T-cells (CD45RA+CD27- and CD45RA+CD27+) persisted until day 180. Within all phenotypic subsets, the T-bet: Eomes ratio tended to be high on day 28 after vaccination and shifted towards predominant Eomes expression on day 180 (median 6.0 (day 28) vs. 2.2 (day 180) p = 0.0625), suggestive of imprinting compatible with long-lived memory properties. YF-tetramer positive CD8+ T-cells were detectable up to 18 years post vaccination, YF-specific antibodies were detectable up to 40 years after single vaccination. Booster vaccination did not increase titers of YF-specific antibodies (mean 12.5 vs. 13.1, p = 0.583), nor induce frequencies or alter phenotypes of YF-tetramer+ CD8+ T-cells.
  
  
  CONCLUSIONS
  The presence of a functionally competent YF-specific memory T-cell pool 18 years and sufficient titers of neutralizing antibodies 35-40 years after first vaccination suggest that single vaccination may be sufficient to provide long-term immunity.
authors.affiliation: Center of Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Division of Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Rosanne W
authors.initials: RW
authors.lastname: Wieten
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Emile F F
authors.initials: EF
authors.lastname: Jonker
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Ester M M
authors.initials: EM
authors.lastname: van Leeuwen
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.|Renal Transplant Unit, Division of Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Ester B M
authors.initials: EB
authors.lastname: Remmerswaal
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.|Renal Transplant Unit, Division of Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Ineke J M
authors.initials: IJ
authors.lastname: Ten Berge
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Adriëtte W
authors.initials: AW
authors.lastname: de Visser
authors.affiliation: Travel Clinic Havenziekenhuis, Rotterdam, the Netherlands.
authors.forename: Perry J J
authors.initials: PJ
authors.lastname: van Genderen
authors.affiliation: Center of Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Division of Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Abraham
authors.initials: A
authors.lastname: Goorhuis
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Leo G
authors.initials: LG
authors.lastname: Visser
authors.affiliation: Center of Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Division of Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Martin P
authors.initials: MP
authors.lastname: Grobusch
authors.affiliation: Center of Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Division of Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.|Amsterdam Institute for Global Health and Development, Amsterdam, the Netherlands.
authors.forename: Godelieve J
authors.initials: GJ
authors.lastname: de Bree
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D006801:Humans; D009500:Neutralization Tests; D011446:Prospective Studies; D010948:Viral Plaque Assay; D022341:Yellow Fever Vaccine / Q000008:administration & dosage* / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D022341:Yellow Fever Vaccine