title: Initial viral load determines the magnitude of the human CD8 T cell response to yellow fever vaccination.
abstract: CD8 T cells are a potent tool for eliminating intracellular pathogens and tumor cells. Thus, eliciting robust CD8 T-cell immunity is the basis for many vaccines under development. However, the relationship between antigen load and the magnitude of the CD8 T-cell response is not well-described in a human immune response. Here we address this issue by quantifying viral load and the CD8 T-cell response in a cohort of 80 individuals immunized with the live attenuated yellow fever vaccine (YFV-17D) by sampling peripheral blood at days 0, 1, 2, 3, 5, 7, 9, 11, 14, 30, and 90. When the virus load was below a threshold (peak virus load < 225 genomes per mL, or integrated virus load < 400 genome days per mL), the magnitude of the CD8 T-cell response correlated strongly with the virus load (R(2) ∼ 0.63). As the virus load increased above this threshold, the magnitude of the CD8 T-cell responses saturated. Recent advances in CD8 T-cell-based vaccines have focused on replication-incompetent or single-cycle vectors. However, these approaches deliver relatively limited amounts of antigen after immunization. Our results highlight the requirement that T-cell-based vaccines should deliver sufficient antigen during the initial period of the immune response to elicit a large number of CD8 T cells that may be needed for protection.
authors.affiliation: Emory Vaccine Center, Department of Microbiology and Immunology.
authors.forename: Rama S
authors.initials: RS
authors.lastname: Akondy
authors.affiliation: Department of Biology and.
authors.forename: Philip L F
authors.initials: PL
authors.lastname: Johnson
authors.affiliation: Emory Vaccine Center, Department of Pathology and Laboratory Medicine, and Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, 05508 Sao Paulo, Brazil.
authors.forename: Helder I
authors.initials: HI
authors.lastname: Nakaya
authors.affiliation: Emory Vaccine Center, Division of Infectious Disease, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322;
authors.forename: Srilatha
authors.initials: S
authors.lastname: Edupuganti
authors.affiliation: Emory Vaccine Center, Division of Infectious Disease, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322;
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Mulligan
authors.affiliation: Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322; and.
authors.forename: Benton
authors.initials: B
authors.lastname: Lawson
authors.affiliation: Emory Vaccine Center.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Miller
authors.affiliation: Emory Vaccine Center, Department of Pathology and Laboratory Medicine, and.
authors.forename: Bali
authors.initials: B
authors.lastname: Pulendran
authors.affiliation: Department of Biology and rahmed@emory.edu rantia@emory.edu.
authors.forename: Rustom
authors.initials: R
authors.lastname: Antia
authors.affiliation: Emory Vaccine Center, Department of Microbiology and Immunology, rahmed@emory.edu rantia@emory.edu.
authors.forename: Rafi
authors.initials: R
authors.lastname: Ahmed
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015331:Cohort Studies; D020869:Gene Expression Profiling; D006801:Humans; D019562:Viral Load; D022341:Yellow Fever Vaccine / Q000276:immunology*; D015005:Yellow fever virus / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification
chemical_list: D022341:Yellow Fever Vaccine
keywords: effector T cells; human CD8 T cells; immune memory; vaccines; viral load