PMID- 26529238
OWN - NLM
STAT- MEDLINE
DCOM- 20160610
LR  - 20240222
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 11
DP  - 2015
TI  - A Phase I, Open-Label Trial, Evaluating the Safety and Immunogenicity of 
      Candidate Tuberculosis Vaccines AERAS-402 and MVA85A, Administered by Prime-Boost 
      Regime in BCG-Vaccinated Healthy Adults.
PG  - e0141687
LID - 10.1371/journal.pone.0141687 [doi]
LID - e0141687
AB  - BACKGROUND: MVA85A and AERAS-402 are two clinically advanced viral vectored TB 
      vaccine candidates expressing Mycobacterium tuberculosis antigens designed to 
      boost BCG-induced immunity. Clinical trials with candidate malaria vaccines have 
      demonstrated that adenoviral vector based priming immunisation, followed by MVA 
      vector boost, induced high levels of immunity. We present the safety and 
      immunogenicity results of the first clinical trial to evaluate this immunisation 
      strategy in TB. METHODS: In this phase 1, open-label trial, 40 healthy previously 
      BCG-vaccinated participants were enrolled into three treatment groups and 
      vaccinated with 1 or 2 doses of AERAS-402 followed by MVA85A; or 3 doses of 
      AERAS-402. RESULTS: Most related adverse events (AEs) were mild and there were no 
      vaccine related serious AEs. Boosting AERAS-402 with MVA85A significantly 
      increased Ag85A-specific T-cell responses from day of vaccination. Two priming 
      doses of AERAS-402 followed by MVA85A boost, resulted in a significantly higher 
      AUC post-peak Ag85A response compared to three doses of AERAS-402 and historical 
      data with MVA85A vaccination alone. The frequency of CD8+ T-cells producing 
      IFN-gamma, TNF-alpha and IL-2 was highest in the group receiving two priming doses of 
      AERAS-402 followed by MVA85A. CONCLUSIONS: Vaccination with AERAS-402 followed by 
      MVA85A was safe and increased the durability of antigen specific T-cell responses 
      and the frequency and polyfunctionality of CD8+ T-cells, which may be important 
      in protection against TB. Further clinical trials with adenoviral prime-MVA85A 
      boost regimens are merited to optimise vaccination intervals, dose and route of 
      immunisation and to evaluate this strategy in the target population in TB high 
      burden countries. TRIAL REGISTRATION: ClinicalTrials.gov NCT01683773.
FAU - Sheehan, Sharon
AU  - Sheehan S
AD  - The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, United Kingdom.
FAU - Harris, Stephanie A
AU  - Harris SA
AD  - The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, United Kingdom.
FAU - Satti, Iman
AU  - Satti I
AD  - The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, United Kingdom.
FAU - Hokey, David A
AU  - Hokey DA
AD  - Aeras Global TB Vaccine Foundation, Rockville, MD, United States of America.
FAU - Dheenadhayalan, Veerabadran
AU  - Dheenadhayalan V
AD  - Aeras Global TB Vaccine Foundation, Rockville, MD, United States of America.
FAU - Stockdale, Lisa
AU  - Stockdale L
AD  - The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, United Kingdom.
FAU - Manjaly Thomas, Zita-Rose
AU  - Manjaly Thomas ZR
AD  - The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, United Kingdom.
FAU - Minhinnick, Alice
AU  - Minhinnick A
AD  - The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, United Kingdom.
FAU - Wilkie, Morven
AU  - Wilkie M
AD  - The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, United Kingdom.
FAU - Vermaak, Samantha
AU  - Vermaak S
AD  - The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, United Kingdom.
FAU - Meyer, Joel
AU  - Meyer J
AD  - The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, United Kingdom.
FAU - O'Shea, Matthew K
AU  - O'Shea MK
AD  - The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, United Kingdom.
FAU - Pau, Maria Grazia
AU  - Pau MG
AD  - Janssen Infectious Diseases and Vaccines (formerly Crucell), Leiden, The 
      Netherlands.
FAU - Versteege, Isabella
AU  - Versteege I
AD  - Janssen Infectious Diseases and Vaccines (formerly Crucell), Leiden, The 
      Netherlands.
FAU - Douoguih, Macaya
AU  - Douoguih M
AD  - Janssen Infectious Diseases and Vaccines (formerly Crucell), Leiden, The 
      Netherlands.
FAU - Hendriks, Jenny
AU  - Hendriks J
AD  - Janssen Infectious Diseases and Vaccines (formerly Crucell), Leiden, The 
      Netherlands.
FAU - Sadoff, Jerald
AU  - Sadoff J
AD  - Janssen Infectious Diseases and Vaccines (formerly Crucell), Leiden, The 
      Netherlands.
FAU - Landry, Bernard
AU  - Landry B
AD  - Aeras Global TB Vaccine Foundation, Rockville, MD, United States of America.
FAU - Moss, Paul
AU  - Moss P
AD  - School of Cancer Sciences, University of Birmingham, Edgbaston, Birmingham, B15 
      2TT, United Kingdom.
FAU - McShane, Helen
AU  - McShane H
AD  - The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, United Kingdom.
LA  - eng
SI  - ClinicalTrials.gov/NCT01683773
GR  - Wellcome Trust/United Kingdom
GR  - 095780/Wellcome Trust/United Kingdom
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151103
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antigens, Bacterial)
RN  - 0 (Cytokines)
RN  - 0 (Tuberculosis Vaccines)
SB  - IM
MH  - *Adenoviridae
MH  - Adolescent
MH  - Adult
MH  - *Antigens, Bacterial/administration & dosage/immunology
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Cytokines/immunology
MH  - Female
MH  - Humans
MH  - *Immunization, Secondary
MH  - Male
MH  - Middle Aged
MH  - Mycobacterium bovis/*immunology
MH  - Mycobacterium tuberculosis/*immunology
MH  - *Tuberculosis Vaccines/administration & dosage/immunology
PMC - PMC4631471
COIS- Competing Interests: MGP, IV, MD, JH and JS are all employees of Janssen, J&J 
      (formerly Crucell). The salaries for these authors were provided by Janssen, J&J 
      (formerly Crucell). Janssen, J&J did not have any additional role in the study 
      design, data collection and analysis, decision to publish, or preparation of the 
      manuscript. This does not alter the authors' adherence to PLOS ONE policies on 
      sharing data and materials. The specific roles of these authors are articulated 
      in the 'author contributions' section. No other authors have conflicts of 
      interest.
EDAT- 2015/11/04 06:00
MHDA- 2016/06/11 06:00
PMCR- 2015/11/03
CRDT- 2015/11/04 06:00
PHST- 2015/07/12 00:00 [received]
PHST- 2015/10/07 00:00 [accepted]
PHST- 2015/11/04 06:00 [entrez]
PHST- 2015/11/04 06:00 [pubmed]
PHST- 2016/06/11 06:00 [medline]
PHST- 2015/11/03 00:00 [pmc-release]
AID - PONE-D-15-25759 [pii]
AID - 10.1371/journal.pone.0141687 [doi]
PST - epublish
SO  - PLoS One. 2015 Nov 3;10(11):e0141687. doi: 10.1371/journal.pone.0141687. 
      eCollection 2015.