A phase I trial evaluating the safety and immunogenicity of a candidate tuberculosis vaccination regimen, ChAdOx1 85A prime - MVA85A boost in healthy UK adults

Research output: Contribution to journalArticle

Authors

  • Morven Wilkie
  • Iman Satti
  • Alice Minhinnick
  • Stephanie Harris
  • Michael Riste
  • Raquel Lopez Ramon
  • Sharon Sheehan
  • Zita-Rose Manjaly Thomas
  • Daniel Wright
  • Lisa Stockdale
  • Ali Hamidi
  • Matthew K O'Shea
  • Kritica Dwivedi
  • Hannah Michaela Behrens
  • Tamara Davenne
  • Joshua Morton
  • Samantha Vermaak
  • Alison Lawrie
  • Helen McShane

Colleges, School and Institutes

External organisations

  • Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK; Department of Oncology, University of Oxford, Oxford, UK.
  • Cancer Immunology and Immunotherapy Centre, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.
  • Univ Birmingham Edgbaston

Abstract

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-γ ELISpot, IgG serum ELISA, and antigen-specific intracellular IFN-γ, TNF-α, 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-γ, TNF-α and IL-2) and IFN-γ+, TNF-α+ 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.

Bibliographic note

Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.

Details

Original languageEnglish
Pages (from-to)779-789
Number of pages11
JournalVaccine
Volume38
Issue number4
Publication statusPublished - 22 Jan 2020