Functional evaluation and genetic evolution of human T-cell responses after vaccination with a conditionally replication-defective cytomegalovirus vaccine
KS Cox, L Zhang, DC Freed, A Tang… - The Journal of …, 2021 - academic.oup.com
KS Cox, L Zhang, DC Freed, A Tang, S Zhang, Y Zhou, IM Wang, RE Rupp, SP Adler…
The Journal of Infectious Diseases, 2021•academic.oup.comBackground 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 …
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 …
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.
Oxford University Press