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

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

来源：Scientific Reports, 2016, 6(1): 36355.

DOI：10.1038/srep36355

<jats:title>Abstract</jats:title><jats:p>The development of a vaccine for <jats:italic>Mycobacterium tuberculosis</jats:italic> (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<jats:sup>+</jats:sup> and CD8<jats:sup>+</jats:sup> T cell responses. However, analysis of the vaccine-induced CD8<jats:sup>+</jats:sup> 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.</jats:p>

• 出版日期2016-11-2