Initial viral load determines the magnitude of the human CD8 T cell response to yellow fever vaccination

• Authors: Rama Akondy, Emory University; Philip L. F. Johnson, Emory University; Helder Nakaya, Emory University; Srilatha Edupuganti, Emory University; Mark Mulligan, Emory University; Benton Lawson, Emory University; Joseph D. Miller, Emory University; Bali Pulendran, Emory University; Rustom Antia, Emory University; Rafi Ahmed, Emory University
• Journal Title: PNAS
• Volume: Volume 112, Number 10
• Publisher: United States National Academy of Sciences | 2015-03-10, Pages 3050-3055
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1073/pnas.1500475112
• Subjects: Biology, Cell; Health Sciences, Immunology; Biology, Microbiology; Health Sciences, Pathology
• Keywords: Science & Technology; Multidisciplinary Sciences; Science & Technology - Other Topics; vaccines; human CD8 T cells; viral load; effector T cells; immune memory; Highly pathogenic SIV; Immune responses; Double-blind; Memory; Antigen; Viremia; Infection; Expansion; Effector; Association

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 (R2 ∼ 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.