Adenovirally-Induced Polyfunctional T Cells Do Not Necessarily Recognize the Infected Target: Lessons from a Phase I Trial of the AERAS-402 Vaccine.
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.
Department of Medicine, Oregon Health and Science University, Portland, Oregon, USA.
Melissa
M
Nyendak
Department of Pediatrics, Oregon Health and Science University, Portland, Oregon, USA.|Department of Medicine, Portland VA Medical Center, Portland, Oregon, USA.
Gwendolyn M
GM
Swarbrick
Department of Pediatrics, Oregon Health and Science University, Portland, Oregon, USA.
Amanda
A
Duncan
Department of Pediatrics, Oregon Health and Science University, Portland, Oregon, USA.
Meghan
M
Cansler
Department of Medicine, Portland VA Medical Center, Portland, Oregon, USA.
Ervina Winata
EW
Huff
Aeras, Rockville, Maryland, USA.
David
D
Hokey
Aeras, Rockville, Maryland, USA.
Tom
T
Evans
Aeras, Rockville, Maryland, USA.
Lewellys
L
Barker
Aeras, Rockville, Maryland, USA.
Gretta
G
Blatner
Janssen Infectious Diseases and Vaccines (formerly Crucell), Leiden, The Netherlands.
Jerald
J
Sadoff
Janssen Infectious Diseases and Vaccines (formerly Crucell), Leiden, The Netherlands.
Macaya
M
Douoguih
Janssen Infectious Diseases and Vaccines (formerly Crucell), Leiden, The Netherlands.
Maria Grazia
MG
Pau
Department of Pediatrics, Oregon Health and Science University, Portland, Oregon, USA.
Deborah A
DA
Lewinsohn
Department of Medicine, Oregon Health and Science University, Portland, Oregon, USA.|Department of Pediatrics, Oregon Health and Science University, Portland, Oregon, USA.|Department of Medicine, Portland VA Medical Center, Portland, Oregon, USA.
David M
DM
Lewinsohn
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D032581:Tuberculosis Vaccines / Q000008:administration & dosage* / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA; D055815:Young Adult
C000592463:AERAS-402; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA