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

2015; National Academy of Sciences; Volume: 112; Issue: 10 Linguagem: Inglês

10.1073/pnas.1500475112

1091-6490

Rama Akondy, Philip L. Johnson, Helder I. Nakaya, Srilatha Edupuganti, Mark J. Mulligan, Benton Lawson, Joseph D. Miller, Bali Pulendran, Rustom Antia, Rafi Ahmed,

Mosquito-borne diseases and control

Significance Current vaccine development against persistent infections such as HIV and tuberculosis focuses on eliciting CD8 T cell immunity through the use of replication-incompetent or single-cycle vectors. Although inherently safe, these vectors deliver limited amounts of antigen. We investigate how antigen load affects the CD8 response by analyzing the viral load and the magnitude of the specific CD8 response after immunization with the live attenuated yellow fever vaccine (YFV-17D). Our results show that the magnitude of the CD8 response is proportional to the amount of antigen when virus load is below a threshold value and saturates above. This finding highlights the requirement that T cell-based vaccines deliver sufficient antigen to elicit a large CD8 response that may be needed for protection.