Heterologous vaccination against human tuberculosis modulates antigen‐specific CD 4 + T ‐cell function

• Published in: European journal of immunology Vol. 43; no. 9; pp. 2409 - 2420
• Main Authors: Dintwe, One B., Day, Cheryl L., Smit, Erica, Nemes, Elisa, Gray, Clive, Tameris, Michele, McShane, Helen, Mahomed, Hassan, Hanekom, Willem A., Scriba, Thomas J.
• Format: Journal Article
• Language: English
• Published: 01.09.2013
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201343454

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 CD 4 + T cells after vaccination with the MVA 85 A vaccine in adults, adolescents, and children. CD 4 + T cells identified with A g85 A peptide‐bearing HLA class II tetramers were characterized by flow cytometry. We also measured proliferative potential and cytokine expression of A g85 A ‐specific CD 4 + T cells. During the effector phase, MVA 85 A ‐induced specific CD 4 + T cells coexpressed IFN ‐γ and IL ‐2, skin homing integrins, and the activation marker CD 38. This was followed by contraction and a transition to predominantly IL ‐2‐expressing, CD 45 RA − CCR 7 + CD 27 + or CD 45 RA + CCR 7 + CD 27 + specific CD 4 + T cells. These surface phenotypes were similar to A g85 A ‐specific T cells prior to MVA 85 A . However, functional differences were observed postvaccination: specific proliferative capacity was markedly higher after 6–12 months than before vaccination. Our data suggest that MVA 85 A vaccination may modulate A g85 A ‐specific CD 4 + 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.