Evaluating aerosol administration of a candidate TB vaccine, MVA85A, as a way to induce potent local cellular immune responses and avoid anti-vector immunity
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.</p