Functional Evaluation and Genetic Evolution of Human T-Cell Responses after Vaccination with a Conditionally Replication-Defective Cytomegalovirus Vaccine

Kara S. Cox, Lu Zhang, Daniel C. Freed, Aimin Tang, Shifang Zhang, Yu Zhou, I. Ming Wang, Richard E. Rupp, Stuart P. Adler, Luwy K. Musey, Dai Wang, Kalpit A. Vora, Tong Ming Fu

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Background: Cytomegalovirus (CMV) can cause congenital infection and is the leading cause of nongenetic newborn disabilities. V160, a conditionally replication-defective virus, is an investigational vaccine under evaluation for prevention of congenital CMV. The vaccine was well tolerated and induced both humoral and cellular immunity in CMV-seronegative trial participants. T-cell-mediated immunity is important for immune control of CMV. Here we describe efforts to understand the quality attributes of the T-cell responses induced by vaccination. Methods: Using multicolor flow cytometry, we analyzed vaccine-induced T cells for memory phenotype, antigen specificity, cytokine profiles, and cytolytic potential. Moreover, antigen-specific T cells were sorted from 4 participants, and next-generation sequencing was used to trace clonal lineage development during the course of vaccination using T-cell receptor β-chain sequences as identifiers. Results: The results demonstrated that vaccination elicited polyfunctional CD4 and CD8 T cells to 2 dominant antigens, pp65 and IE1, with a predominantly effector phenotype. Analysis of T-cell receptor repertoires showed polyclonal expansion of pp65-and IE1-specific T cells after vaccination. Conclusion: V160 induced a genetically diverse and polyfunctional T-cell response and the data support further clinical development of V160 for prevention of CMV infection and congenital transmission. Clinical Trials Registration: NCT01986010.

Original languageEnglish (US)
Pages (from-to)2001-2012
Number of pages12
JournalJournal of Infectious Diseases
Volume223
Issue number11
DOIs
StatePublished - Jun 1 2021

Keywords

  • CMV
  • T-cell
  • cytomegalovirus
  • vaccine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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