title: A first-in-human phase 1 trial to evaluate the safety and immunogenicity of the candidate tuberculosis vaccine MVA85A-IMX313, administered to BCG-vaccinated adults.
abstract: BACKGROUND
  There is an urgent need for a new and effective tuberculosis vaccine because BCG does not sufficiently prevent pulmonary disease. IMX313 is a novel carrier protein designed to improve cellular and humoral immunity. MVA85A-IMX313 is a novel vaccine candidate designed to boost immunity primed by bacillus Calmette-Guérin (BCG) that has been immunogenic in pre-clinical studies. This is the first evaluation of IMX313 delivered as MVA85A-IMX313 in humans.
  
  
  METHODS
  In this phase 1, open-label first-in-human trial, 30 healthy previously BCG-vaccinated adults were enrolled into three treatment groups and vaccinated with low dose MVA85A-IMX313 (group A), standard dose MVA85A-IMX313 (group B), or MVA85A (group C). Volunteers were followed up for 6 months for safety and immunogenicity assessment.
  
  
  RESULTS
  The majority of adverse events were mild and there were no vaccine-related serious AEs. Both MVA85A-IMX313 and MVA85A induced a significant increase in IFN-γ ELISpot responses. There were no significant differences between the Ag85A ELISpot and intracellular cytokine responses between the two study groups B (MVA85A-IMX313) and C (MVA85A) at any time point post-vaccination.
  
  
  CONCLUSIONS
  MVA85A-IMX313 was well tolerated and immunogenic. There was no significant difference in the number of vaccine-related, local or systemic adverse reactions between MVA85A and MVA85A-IMX313 groups. The mycobacteria-specific cellular immune responses induced by MVA85A-IMX313 were not significantly different to those detected in the MVA85A group. In light of this encouraging safety data, further work to improve the potency of molecular adjuvants like IMX313 is merited. This trial was registered on clinicatrials.gov ref. NCT01879163.
authors: The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
authors: Alice
authors: A
authors: Minhinnick
authors: The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
authors: Iman
authors: I
authors: Satti
authors: The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
authors: Stephanie
authors: S
authors: Harris
authors: The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
authors: Morven
authors: M
authors: Wilkie
authors: The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
authors: Sharon
authors: S
authors: Sheehan
authors: The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
authors: Lisa
authors: L
authors: Stockdale
authors: The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
authors: Zita-Rose
authors: ZR
authors: Manjaly Thomas
authors: The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
authors: Raquel
authors: R
authors: Lopez-Ramon
authors: The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
authors: Ian
authors: I
authors: Poulton
authors: The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
authors: Alison
authors: A
authors: Lawrie
authors: The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
authors: Samantha
authors: S
authors: Vermaak
authors: IMAXIO, 99, rue de Gerland, 69007 Lyon, France.
authors: Alexandre
authors: A
authors: Le Vert
authors: IMAXIO, 99, rue de Gerland, 69007 Lyon, France.
authors: Judith
authors: J
authors: Del Campo
authors: IMAXIO, 99, rue de Gerland, 69007 Lyon, France.
authors: Fergal
authors: F
authors: Hill
authors: School of Cancer Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors: Paul
authors: P
authors: Moss
authors: The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK. Electronic address: helen.mcshane@ndm.ox.ac.uk.
authors: Helen
authors: H
authors: McShane
mesh_terms: D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D001500:BCG Vaccine / Q000008:administration & dosage; D016207:Cytokines / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D014376:Tuberculosis / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D019444:Vaccines, DNA; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D001500:BCG Vaccine; D016207:Cytokines; D007074:Immunoglobulin G; C549320:MVA 85A; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA
keywords: IMX313; Immunogenicity; MVA85A; Tuberculosis; Vaccine