Adenovirally-Induced Polyfunctional T Cells Do Not Necessarily Recognize the Infected Target: Lessons from a Phase I Trial of the AERAS-402 Vaccine

Melissa Nyendak, Gwendolyn M. Swarbrick, Amanda Duncan, Meghan Cansler, Ervina Winata Huff, David Hokey, Tom Evans, Lewellys Barker, Gretta Blatner, Jerald Sadoff, Macaya Douoguih, Maria Grazia Pau, Deborah Lewinsohn, David Lewinsohn

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7 Scopus citations

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.

Original languageEnglish (US)
Article number36355
JournalScientific Reports
Volume6
DOIs
StatePublished - Nov 2 2016

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    Nyendak, M., Swarbrick, G. M., Duncan, A., Cansler, M., Huff, E. W., Hokey, D., Evans, T., Barker, L., Blatner, G., Sadoff, J., Douoguih, M., Pau, M. G., Lewinsohn, D., & Lewinsohn, D. (2016). Adenovirally-Induced Polyfunctional T Cells Do Not Necessarily Recognize the Infected Target: Lessons from a Phase I Trial of the AERAS-402 Vaccine. Scientific Reports, 6, [36355]. https://doi.org/10.1038/srep36355