Prime–boost approaches to tuberculosis vaccine development

Abstract

Four individuals die from active TB disease each minute, while at least 2 billion are latently infected and at risk for disease reactivation. BCG, the only licensed TB vaccine, is effective in preventing childhood forms of TB; however its poor efficacy in adults, emerging drug-resistant TB strains and tedious chemotherapy regimes, warrant the development of novel prophylactic measures. Designing safe and effective vaccines against TB will require novel approaches on several levels, including the administration of rationally selected mycobacterial antigens in efficient delivery vehicles via optimal immunization routes. Given the primary site of disease manifestation in the lungs, development of mucosal immunization strategies to generate protective immune responses both locally, and in the circulation, may be important for effective TB prophylaxis. This review focuses on prime–boost immunization strategies currently under investigation and highlights the potential of mucosal delivery and rational vaccine design based on systems biology.

Keywords::

• BCG
• lung immunity
• mucosal delivery
• prime–boost
• recombinant viral vectors
• systems biology
• tuberculosis
• T cell
• vaccine

Financial & competing interests disclosure

This work was supported by NIH grants 5R01AI058810, 3R01AI058810-06S2, and 2P01 HL076100 (AJ Ramsay) and the Louisiana Vaccine Center funded by the Louisiana Board of Regents. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.