Phase I Trial Evaluating the Safety and Immunogenicity of Candidate TB Vaccine MVA85A, Delivered by Aerosol to Healthy M.tb-Infected Adults

Vaccines

Martin Dedicoat¹  Fergus Gleeson²  Paul Moss³  ChristopherP. Conlon⁴  Henry Bettinson⁵  Felicity Perrin⁶  Marc Lipman⁷  Catherine Cosgrove⁸  Helen McShane⁹  Rebecca Powell Doherty⁹  Alison Lawrie⁹  Morven Wilkie⁹  Rachel Wittenberg⁹  Iman Satti⁹  JuliaL. Marshall⁹  Samantha Vermaak⁹  StephanieA. Harris⁹  Michael Riste⁹  Danny Wright⁹  Raquel Lopez Ramon⁹ 

[1] Department of Infection and Tropical Medicine, Heartlands Hospital, Birmingham B9 5SS, UK;Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK;Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK;Nuffield Department of Medicine, University of Oxford, Oxford OX3 7DQ, UK;Oxford Centre for Respiratory Medicine, Oxford University Hospitals NHS Trust, Oxford OX3 7LE, UK;Respiratory Medicine, King’s College Hospital NHS Foundation Trust, London SE5 9PJ, UK;Royal Free London NHS Foundation Trust, London NW3 2QG, UK;TB Chest Clinic, St George’s University Hospitals NHS Foundation Trust, London SW15 5PN, UK;The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK;

关键词: aerosol vaccine;    MVA85A;    mycobacteria;    latent TB infection;   

DOI  :  10.3390/vaccines9040396

来源: DOAJ

【 摘 要 】

The immunogenicity of the candidate tuberculosis (TB) vaccine MVA85A may be enhanced by aerosol delivery. Intradermal administration was shown to be safe in adults with latent TB infection (LTBI), but data are lacking for aerosol-delivered candidate TB vaccines in this population. We carried out a Phase I trial to evaluate the safety and immunogenicity of MVA85A delivered by aerosol in UK adults with LTBI (NCT02532036). Two volunteers were recruited, and the vaccine was well-tolerated with no safety concerns. Aerosolised vaccination with MVA85A induced mycobacterium- and vector-specific IFN-γ in blood and mycobacterium-specific Th1 cytokines in bronchoalveolar lavage. We identified several important barriers that could hamper recruitment into clinical trials in this patient population. The trial did not show any safety concerns in the aerosol delivery of a candidate viral-vectored TB vaccine to two UK adults with Mycobacterium tuberculosis (M.tb) infection. It also systemically and mucosally demonstrated inducible immune responses following aerosol vaccination. A further trial in a country with higher incidence of LTBI would confirm these findings.

【 授权许可】

Unknown