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

Research output: Contribution to journalArticle

4 Citations (Scopus)

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

Fingerprint

Vaccines
T-Lymphocytes
Mycobacterium tuberculosis
Vaccination
Mycobacterium bovis
Adenoviridae
AERAS-402
Biomedical Research
Immunity
Randomized Controlled Trials
Placebos
Antigens
DNA
Proteins

ASJC Scopus subject areas

  • General

Cite this

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

In: Scientific Reports, Vol. 6, 36355, 02.11.2016.

Research output: Contribution to journalArticle

Nyendak, M, Swarbrick, GM, Duncan, A, Cansler, M, Huff, EW, Hokey, D, Evans, T, Barker, L, Blatner, G, Sadoff, J, Douoguih, M, Pau, MG, 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, vol. 6, 36355. https://doi.org/10.1038/srep36355
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 ; Lewinsohn, David. / Adenovirally-Induced Polyfunctional T Cells Do Not Necessarily Recognize the Infected Target : Lessons from a Phase I Trial of the AERAS-402 Vaccine. In: Scientific Reports. 2016 ; Vol. 6.
@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 Deborah Lewinsohn and David Lewinsohn",
year = "2016",
month = "11",
day = "2",
doi = "10.1038/srep36355",
language = "English (US)",
volume = "6",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Adenovirally-Induced Polyfunctional T Cells Do Not Necessarily Recognize the Infected Target

T2 - Lessons from a Phase I Trial of the AERAS-402 Vaccine

AU - Nyendak, Melissa

AU - Swarbrick, Gwendolyn M.

AU - Duncan, Amanda

AU - Cansler, Meghan

AU - Huff, Ervina Winata

AU - Hokey, David

AU - Evans, Tom

AU - Barker, Lewellys

AU - Blatner, Gretta

AU - Sadoff, Jerald

AU - Douoguih, Macaya

AU - Pau, Maria Grazia

AU - Lewinsohn, Deborah

AU - Lewinsohn, David

PY - 2016/11/2

Y1 - 2016/11/2

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84994314457&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84994314457&partnerID=8YFLogxK

U2 - 10.1038/srep36355

DO - 10.1038/srep36355

M3 - Article

C2 - 27805026

AN - SCOPUS:84994314457

VL - 6

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 36355

ER -