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Title: Evaluating aerosol administration of a candidate TB vaccine, MVA85A, as a way to induce potent local cellular immune responses and avoid anti-vector immunity
Author: Thomas, Zita-Rose Manjaly
ISNI:       0000 0004 6495 2465
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2016
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There is an urgent need for a better vaccine against TB than BCG, which confers variable protection against pulmonary TB. Heterologous prime-boost regimens with viral vector vaccines are a leading strategy for TB vaccine development. MVA85A is a viral vector candidate TB vaccine designed to boost BCG. This phase I clinical trial was designed to evaluate whether alternating aerosol and intradermal routes of vaccination can improve Ag85A immunogenicity; maybe by circumventing local anti- MVA immunity. Thirty-six BCG-vaccinated healthy UK adults received two MVA85A vaccinations one month apart as heterologous (aerosol-intradermal or intradermalaerosol) or homologous prime-boost (intradermal-intradermal). Bronchoscopies with bronchoalveolar lavages (BAL) were performed 7 days after each vaccination. Delivering MVA85A by aerosol as a priming immunisation was well tolerated and highly immunogenic. Boosting an intradermal MVA85A prime with an aerosolised MVA85A vaccination led to transient respiratory and systemic adverse events which resulted in vaccinations in this group ceasing. Aerosolised MVA85A induced potent Ag85A-specific T cell responses in mucosal and systemic compartments; and suggested a potential for dose sparing with this route. The intradermal-aerosol regimen boosted Ag85A-specific cellular immune responses in systemic and lung mucosal compartments. Serum antibodies to Ag85A and MVA were only detected after intradermal vaccination. Anti-Ag85A antibodies in serum were boosted by a second intradermal vaccination. The findings of this trial are important for the development of aerosolised TB vaccines but also for new viral vector vaccines for other respiratory pathogens.
Supervisor: McShane, Helen ; Satti, Iman ; Bettinson, Henry Sponsor: NIHR Oxford Biomedical Research Centre ; Wellcome Trust
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available