@article{b433ec15ab9f45eb93545d98691cd15e,
title = "Adenovirally-Induced Polyfunctional T Cells Do Not Necessarily Recognize the Infected Target: Lessons from a Phase I Trial of the AERAS-402 Vaccine",
abstract = "The development of a vaccine for Mycobacterium tuberculosis (Mtb) has been impeded by the absence of correlates of protective immunity. One correlate would be the ability of cells induced by vaccination to recognize the Mtb-infected cell. AERAS-402 is a replication-deficient serotype 35 adenovirus containing DNA expressing a fusion protein of Mtb antigens 85A, 85B and TB10.4. We undertook a phase I double-blind, randomized placebo controlled trial of vaccination with AERAS-402 following BCG. Analysis of the vaccine-induced immune response revealed strong antigen-specific polyfunctional CD4+ and CD8+T cell responses. However, analysis of the vaccine-induced CD8+T cells revealed that in many instances these cells did not recognize the Mtb-infected cell. Our findings highlight the measurement of vaccine-induced, polyfunctional T cells may not reflect the extent or degree to which these cells are capable of identifying the Mtb-infected cell and correspondingly, the value of detailed experimental medicine studies early in vaccine development.",
author = "Melissa Nyendak and Swarbrick, {Gwendolyn M.} and Amanda Duncan and Meghan Cansler and Huff, {Ervina Winata} and David Hokey and Tom Evans and Lewellys Barker and Gretta Blatner and Jerald Sadoff and Macaya Douoguih and Pau, {Maria Grazia} and Lewinsohn, {Deborah A.} and Lewinsohn, {David M.}",
note = "Funding Information: The authors acknowledge the contributions of Sean Bennett MD (AERAS), Melissa Kumagai, Phyllis Carello and staff from the Oregon Clinical and Translational Institute at Oregon Health and Science University, and Erin Merrifield (OHSU) for IRB support. We also acknowledge Jenny Hendriks and Maria Grazia Pau for review of the manuscript. We thank the study participants without whom this study would not be possible. This work was supported by the following agency and institutes: the Aeras Global Tuberculosis Vaccine Foundation, NIH contract, HHSN272200900053C, and the NIH National Center for Research Resources grant KL2RR02414 (MN). This work was also supported by Merit Review Awards I01 BX000533 (DML) from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development and resources and the use of facilities at the VA Portland Health Care System and from the NIH R01 AI048090 (DML); The contents of this manuscript do not represent the views of the U.S. Department of Veterans Affairs or the United States Government. Publisher Copyright: {\textcopyright} The Author(s) 2016.",
year = "2016",
month = nov,
day = "2",
doi = "10.1038/srep36355",
language = "English (US)",
volume = "6",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
}