Transcriptional signature of durable effector T cells elicited by a replication defective HCMV vaccine

Xiaohua Ye, David J.H. Shih, Zhiqiang Ku, Junping Hong, Diane F. Barrett, Richard E. Rupp, Ningyan Zhang, Tong Ming Fu, W. Jim Zheng, Zhiqiang An

Research output: Contribution to journalArticlepeer-review

Abstract

Human cytomegalovirus (HCMV) is a leading infectious cause of birth defects and the most common opportunistic infection that causes life-threatening diseases post-transplantation; however, an effective vaccine remains elusive. V160 is a live-attenuated replication defective HCMV vaccine that showed a 42.4% efficacy against primary HCMV infection among seronegative women in a phase 2b clinical trial. Here, we integrated the multicolor flow cytometry, longitudinal T cell receptor (TCR) sequencing, and single-cell RNA/TCR sequencing approaches to characterize the magnitude, phenotype, and functional quality of human T cell responses to V160. We demonstrated that V160 de novo induces IE-1 and pp65 specific durable polyfunctional effector CD8 T cells that are comparable to those induced by natural HCMV infection. We identified a variety of V160-responsive T cell clones which exhibit distinctive “transient” and “durable” expansion kinetics, and revealed a transcriptional signature that marks durable CD8 T cells post-vaccination. Our study enhances the understanding of human T-cell immune responses to V160 vaccination.

Original languageEnglish (US)
Article number70
Journalnpj Vaccines
Volume9
Issue number1
DOIs
StatePublished - Dec 2024

ASJC Scopus subject areas

  • Immunology
  • Pharmacology
  • Infectious Diseases
  • Pharmacology (medical)

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