Inhaled vaccines for the prevention of tuberculosis

Abstract

Tuberculosis a major challenge to global health exacerbated by emerging multi drug resistant (MDR) and
extensively drug resistant (X-DR) strains of M. tuberculosis and co-infection with HIV. BCG, the only approved
vaccine, has variable protection ranging between 0-80%. Compared to the large number of new vaccine candidates
a modest effort has been expended to investigate other routes of administration, such as pulmonary and intranasal.
Vaccination by these routes is relevant since TB infection is mainly acquired by inhalation of a few aerosol
droplets containing as little as 3-5 viable bacilli. The lungs have many attractive immunological features including
bronchoalveolar lymphoid tissue (BALT) and local antigen presenting cells (APCs) sampling airborne pathogens.
Aerosol vaccination is a noninvasive method of antigen delivery that may facilitate mass vaccination campaigns.
Administration by non-medical personnel and the ability to eliminate transmission of blood borne diseases arising
from poor practice in injected procedures in remote areas is beneficial. The current dogma does not include mucosal
immunity for protection against TB but its contribution may not be ruled out. The selection of the appropriate antigen,
aerosol formulation and inhaler will determine the success of this approach. Dry powder formulations of antigen/
adjuvant combinations have efficiency of delivery, stability and sterility advantages over liquid formulations. Dry
powder vaccines can be manufactured as micro particles and nanoparticles prepared with different materials
including polymers, sugars and amino acids. Examples of these novel vaccine formulations and their evaluation in
animal models are discussed in the present review. The proposed pharmaceutical and clinical advantages of inhaled
dry powder vaccines justify further evaluation.