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- Title
Functional Evaluation and Genetic Evolution of Human T-Cell Responses After Vaccination With a Conditionally Replication-Defective Cytomegalovirus Vaccine.
- Authors
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; Fu, Tong-Ming
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusion: </bold>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.<bold>Clinical Trials Registration: </bold>NCT01986010.
- Subjects
CELLULAR immunity; HUMORAL immunity; VACCINATION; HUMAN evolution; CLINICAL trial registries; CYTOMEGALOVIRUSES; CYTOMEGALOVIRUS diseases
- Publication
Journal of Infectious Diseases, 2021, Vol 223, Issue 11, p2001
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jiaa631