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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-12

AUTHORS

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 A Lewinsohn, David M Lewinsohn

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. More... »

PAGES

36355

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/srep36355

DOI

http://dx.doi.org/10.1038/srep36355

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1024003412

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27805026


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