Functional Evaluation and Genetic Evolution of Human T-Cell Responses After Vaccination With a Conditionally Replication-Defective Cytomegalovirus Vaccine.

Autor:	Cox KS; Department of Infectious Diseases and Vaccines, Merck & Co., Inc. Kenilworth, New Jersey, USA., Zhang L; Department of Strategic Planning and Research Informatics, MSD, Beijing, China., Freed DC; Department of Infectious Diseases and Vaccines, Merck & Co., Inc. Kenilworth, New Jersey, USA., Tang A; Department of Infectious Diseases and Vaccines, Merck & Co., Inc. Kenilworth, New Jersey, USA., Zhang S; Abhelix, LLC., South Plainfield, New Jersey, USA., Zhou Y; Department of Infectious Diseases and Vaccines, Merck & Co., Inc. Kenilworth, New Jersey, USA., Wang IM; Department of Genetics and Pharmacogenomics, Merck & Co., Inc. Kenilworth, New Jersey, USA., Rupp RE; Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, Texas, USA., Adler SP; CMV Research Foundation, Richmond, Virginia, USA., Musey LK; Department of Clinical Research, Merck & Co., Inc. Kenilworth, New Jersey, USA., Wang D; Department of Infectious Diseases and Vaccines, Merck & Co., Inc. Kenilworth, New Jersey, USA., Vora KA; Department of Infectious Diseases and Vaccines, Merck & Co., Inc. Kenilworth, New Jersey, USA., Fu TM; Department of Infectious Diseases and Vaccines, Merck & Co., Inc. Kenilworth, New Jersey, USA.
Jazyk:	angličtina
Zdroj:	The Journal of infectious diseases [J Infect Dis] 2021 Jun 04; Vol. 223 (11), pp. 2001-2012.
DOI:	10.1093/infdis/jiaa631
Abstrakt:	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. (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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