There is an urgent need for a better vaccine against TB than BCG, which confers variable protection against pulmonary TB, the main source of TB transmission.

Heterologous prime-boost vaccination regimens using virally-vectored vaccines induce strong cellular immune responses and are a leading strategy for TB vaccine development. Boosting BCG with MVA85A, a recombinant viral vector expressing antigen 85A, can enhance BCG induced protection in animal models. MVA85A in humans is safe and immunogenic when administered systemically.

Animal data suggests delivering a vaccine to the respiratory mucosa may be the most protective route. We recently completed the first trial where a virally-vectored vaccine, MVA85A, was delivered to humans by aerosol; and was found to be safe and highly immunogenic. This route also has potential for dose-sparing.

A limitation of virally-vectored vaccines is anti-vector immunity, which limits use and re-use.

Non-human primate data with aerosolised MVA85A suggests that aerosol vaccination induces less systemic anti-vector immunity than systemic routes. We have demonstrated this is also true in humans in our first aerosol trial, where humoral anti-vector immunity to MVA was induced by volunteers vaccinated by the systemic route but not the aerosol route.

An on-going trial now addresses the question, if alternating routes of vaccination can abrogate anti-vector immunity, by immunising twice with MVA85A by heterologous routes one month apart.

This would be an important development for the development of aerosolised TB vaccines but also for new vectored vaccines for RSV, universal influenza and a range of bacterial respiratory pathogens.