Should a new tuberculosis vaccine be administered intranasally?

Most of the world's population is vaccinated with the only available vaccine against tuberculosis (TB), the Bacillus Calmette-Guérin (BCG) vaccine that was developed almost a century ago. Despite the wide coverage of the BCG vaccine, there are great variations in protective efficacy among different study populations. BCG vaccination protects against childhood forms of TB, but this immunity wanes with age, resulting in none, or insufficient, protection against adult pulmonary TB (PTB). PTB is the major disease manifestation of TB in adults and it causes death at the most productive age, further adding to poverty in already impoverished countries. Therefore, new more effective vaccines and novel immunisation strategies are urgently needed. The most common route of TB is by inhalation of tubercle bacilli leading to the establishment of a primary infection in the lung. Immunising through the nasal mucosal surface should therefore have advantage over other routes, as such vaccine administration elicits protective immune responses also in the lung, i.e. at the site of primary infection. Several new TB-vaccine candidates have been evaluated for their protective efficacy in animal models using the mucosal route of immunisation. In formulating such vaccines, the adjuvants and delivery systems are crucially important.