Transcriptional Signature of Durable Effector T Cells Elicited By A Replication Defective HCMV Vaccine

Authors

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

Publication Date

4-1-2024

Journal

NPJ Vaccines

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.

Keywords

Live attenuated vaccines, Viral infection, Immunological memory

DOI

10.1038/s41541-024-00860-w

PMID

38561339

PMCID

PMC10984989

PubMedCentral® Posted Date

April 2024

PubMedCentral® Full Text Version

Post-Print

Published Open-Access

yes