1. Functional Evaluation and Genetic Evolution of Human T-Cell Responses After Vaccination With a Conditionally Replication-Defective Cytomegalovirus Vaccine.
- Author
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Cox, Kara S, Zhang, Lu, Freed, Daniel C, Tang, Aimin, Zhang, Shifang, Zhou, Yu, Wang, I-Ming, Rupp, Richard E, Adler, Stuart P, Musey, Luwy K, Wang, Dai, Vora, Kalpit A, and Fu, Tong-Ming
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CELLULAR immunity , *HUMORAL immunity , *VACCINATION , *HUMAN evolution , *CLINICAL trial registries , *CYTOMEGALOVIRUSES , *CYTOMEGALOVIRUS diseases - 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. [ABSTRACT FROM AUTHOR]- Published
- 2021
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