PMID- 31735500
OWN - NLM
STAT- MEDLINE
DCOM- 20210210
LR  - 20211204
IS  - 1873-2518 (Electronic)
IS  - 0264-410X (Print)
IS  - 0264-410X (Linking)
VI  - 38
IP  - 4
DP  - 2020 Jan 22
TI  - A phase I trial evaluating the safety and immunogenicity of a candidate 
      tuberculosis vaccination regimen, ChAdOx1 85A prime - MVA85A boost in healthy UK 
      adults.
PG  - 779-789
LID - S0264-410X(19)31504-X [pii]
LID - 10.1016/j.vaccine.2019.10.102 [doi]
AB  - BACKGROUND: This phase I trial evaluated the safety and immunogenicity of a 
      candidate tuberculosis vaccination regimen, ChAdOx1 85A prime-MVA85A boost, 
      previously demonstrated to be protective in animal studies, in healthy UK adults. 
      METHODS: We enrolled 42 healthy, BCG-vaccinated adults into 4 groups: low dose 
      Starter Group (n = 6; ChAdOx1 85A alone), high dose groups; Group A (n = 12; 
      ChAdOx1 85A), Group B (n = 12; ChAdOx1 85A prime - MVA85A boost) or Group C 
      (n = 12; ChAdOx1 85A - ChAdOx1 85A prime - MVA85A boost). Safety was determined 
      by collection of solicited and unsolicited vaccine-related adverse events (AEs). 
      Immunogenicity was measured by antigen-specific ex-vivo IFN-gamma ELISpot, IgG serum 
      ELISA, and antigen-specific intracellular IFN-gamma, TNF-alpha, IL-2 and IL-17. RESULTS: 
      AEs were mostly mild/moderate, with no Serious Adverse Events. ChAdOx1 85A 
      induced Ag85A-specific ELISpot and intracellular cytokine CD4+ and CD8+ T cell 
      responses, which were not boosted by a second dose, but were boosted with MVA85A. 
      Polyfunctional CD4+ T cells (IFN-gamma, TNF-alpha and IL-2) and IFN-gamma+, TNF-alpha+ CD8+ T 
      cells were induced by ChAdOx1 85A and boosted by MVA85A. ChAdOx1 85A induced 
      serum Ag85A IgG responses which were boosted by MVA85A. CONCLUSION: A ChAdOx1 85A 
      prime - MVA85A boost is well tolerated and immunogenic in healthy UK adults.
CI  - Copyright (c) 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Wilkie, Morven
AU  - Wilkie M
AD  - The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
FAU - Satti, Iman
AU  - Satti I
AD  - The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
FAU - Minhinnick, Alice
AU  - Minhinnick A
AD  - The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
FAU - Harris, Stephanie
AU  - Harris S
AD  - The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
FAU - Riste, Michael
AU  - Riste M
AD  - The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
FAU - Ramon, Raquel Lopez
AU  - Ramon RL
AD  - The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
FAU - Sheehan, Sharon
AU  - Sheehan S
AD  - The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
FAU - Thomas, Zita-Rose Manjaly
AU  - Thomas ZM
AD  - The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
FAU - Wright, Daniel
AU  - Wright D
AD  - The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
FAU - Stockdale, Lisa
AU  - Stockdale L
AD  - The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
FAU - Hamidi, Ali
AU  - Hamidi A
AD  - The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
FAU - O'Shea, Matthew K
AU  - O'Shea MK
AD  - The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
FAU - Dwivedi, Kritica
AU  - Dwivedi K
AD  - The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
FAU - Behrens, Hannah Michaela
AU  - Behrens HM
AD  - The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
FAU - Davenne, Tamara
AU  - Davenne T
AD  - The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
FAU - Morton, Joshua
AU  - Morton J
AD  - The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
FAU - Vermaak, Samantha
AU  - Vermaak S
AD  - The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
FAU - Lawrie, Alison
AU  - Lawrie A
AD  - The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
FAU - Moss, Paul
AU  - Moss P
AD  - Institute of Immunology and Immunotherapy, University of Birmingham, Edgbaston, 
      Birmingham B15 2TT, UK.
FAU - McShane, Helen
AU  - McShane H
AD  - The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK. Electronic 
      address: helen.mcshane@ndm.ox.ac.uk.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20191115
PL  - Netherlands
TA  - Vaccine
JT  - Vaccine
JID - 8406899
RN  - 0 (BCG Vaccine)
RN  - 0 (Cytokines)
RN  - 0 (MVA 85A)
RN  - 0 (Tuberculosis Vaccines)
RN  - 0 (Vaccines, DNA)
SB  - IM
MH  - Adult
MH  - BCG Vaccine/*administration & dosage/immunology
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Cytokines/immunology
MH  - Follow-Up Studies
MH  - Humans
MH  - Immunization, Secondary
MH  - Immunogenicity, Vaccine
MH  - Tuberculosis/immunology/*prevention & control
MH  - Tuberculosis Vaccines/*administration & dosage/adverse effects/immunology
MH  - United Kingdom
MH  - Vaccination/adverse effects/*methods
MH  - Vaccines, DNA
PMC - PMC6985898
OTO - NOTNLM
OT  - ChAdOx1 85A
OT  - Immunogenicity
OT  - MVA85A
OT  - Safety
OT  - Tuberculosis
OT  - Vaccine
COIS- The authors declare that they have no known competing financial interests or 
      personal relationships that could have appeared to influence the work reported in 
      this paper.
EDAT- 2019/11/19 06:00
MHDA- 2021/02/11 06:00
PMCR- 2020/01/22
CRDT- 2019/11/19 06:00
PHST- 2019/06/20 00:00 [received]
PHST- 2019/10/30 00:00 [revised]
PHST- 2019/10/31 00:00 [accepted]
PHST- 2019/11/19 06:00 [pubmed]
PHST- 2021/02/11 06:00 [medline]
PHST- 2019/11/19 06:00 [entrez]
PHST- 2020/01/22 00:00 [pmc-release]
AID - S0264-410X(19)31504-X [pii]
AID - 10.1016/j.vaccine.2019.10.102 [doi]
PST - ppublish
SO  - Vaccine. 2020 Jan 22;38(4):779-789. doi: 10.1016/j.vaccine.2019.10.102. Epub 2019 
      Nov 15.