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Heterologous prime-boost strategies hold promise for vaccination against tuberculosis. However, the T-cell characteristics required for protection are not known. We proposed that boost vaccines should induce long-lived functional and phenotypic changes to T cells primed by Bacille Calmette Guerin (BCG) and/or natural exposure to mycobacteria. We characterized changes among specific CD4(+) T cells after vaccination with the MVA85A vaccine in adults, adolescents, and children. CD4(+) T cells identified with Ag85A peptide-bearing HLA class II tetramers were characterized by flow cytometry. We also measured proliferative potential and cytokine expression of Ag85A-specific CD4(+) T cells. During the effector phase, MVA85A-induced specific CD4(+) T cells coexpressed IFN-γ and IL-2, skin homing integrins, and the activation marker CD38. This was followed by contraction and a transition to predominantly IL-2-expressing, CD45RA(-) CCR7(+) CD27(+) or CD45RA(+) CCR7(+) CD27(+) specific CD4(+) T cells. These surface phenotypes were similar to Ag85A-specific T cells prior to MVA85A. However, functional differences were observed postvaccination: specific proliferative capacity was markedly higher after 6-12 months than before vaccination. Our data suggest that MVA85A vaccination may modulate Ag85A-specific CD4(+) T-cell function, resulting in greater recall potential. Importantly, surface phenotypes commonly used as proxies for memory T-cell function did not associate with functional effects of vaccination.

Original publication

DOI

10.1002/eji.201343454

Type

Journal article

Journal

Eur J Immunol

Publication Date

09/2013

Volume

43

Pages

2409 - 2420

Keywords

HLA class II tetramer, MVA85A, Proliferation, T cells, Vaccine, ADP-ribosyl Cyclase 1, Acyltransferases, Adolescent, Adult, Antigens, Bacterial, CD4-Positive T-Lymphocytes, Cell Proliferation, Child, Child, Preschool, Female, Humans, Immunologic Memory, Interferon-gamma, Interleukin-2, Leukocyte Common Antigens, Lymphocyte Activation, Male, Middle Aged, Mycobacterium tuberculosis, Receptors, CCR7, Tuberculosis, Tuberculosis Vaccines, Tumor Necrosis Factor Receptor Superfamily, Member 7, Viral Vaccines, Young Adult