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.
Highlights
Mycobacterium tuberculosis (MTB) is one of the most prominent human pathogens infecting one-third of the world’s population [1] and mutates into multidrug-resistant (MDR) and extensively-drug resistant (XDR) strains
Infection with and mutation of MTB, the co-infection with the human immunodeficiency virus (HIV), the limitation in current therapies and the lack of patient compliance for tuberculosis (TB) treatment have all contributed to the significant threat to the global control of TB
This review presents the factors that can influence the successful delivery and effectiveness of an inhaled vaccine for tuberculosis including the type of vaccine or antigen used, the relationship between the route of immunization and the nature of the immune response elicited, the formulation and the device employed to deliver the vaccine and the animal model in which the vaccine is tested
Summary
Mycobacterium tuberculosis (MTB) is one of the most prominent human pathogens infecting one-third of the world’s population [1] and mutates into multidrug-resistant (MDR) and extensively-drug resistant (XDR) strains. A single intranasal but not IM immunization was able to induce potent protection from MTB challenge in a mouse model used to boost mice primed with SC BCG, showing enhanced protection that was correlated with the numbers of IFN-gamma CD4+ and CD8+ in airway lumen
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