New vaccines in development and future direction
McShane H., Rowland R.
© 2011 Future Medicine Ltd. All rights reserved. The effectiveness of Bacillus Calmette-Guérin (BCG) vaccine in childhood suggests successful vaccination against TB is possible, but the incomplete protection and safety concerns highlight the need for a new TB vaccine. Recombinant BCG vaccines are designed with the rationale of improving upon the efficacy of BCG against systemic disease while addressing the reasons for its limited protection against pulmonary disease. Deleting essential virulence genes from Mycobacterium tuberculosis is an alternative approach to developing recombinant BCG vaccines. Recombinant viral vectors, such as poxviruses and adenoviruses, are a technology with the capacity for cloning large or multiple immunodominant antigens and can be manufactured to high titers, allowing easy scale-up of vaccine production. The recent development of a number of candidate immunostimulant adjuvants that induce cell-mediated immunity has made a protein-adjuvant subunit TB vaccine a feasible approach. At present, the most advanced TB candidates have progressed to PhaseII safety and immunogenicity studies in target populations, with two candidates being evaluated in efficacytrials. There is a major requirement for new TB vaccine trial sites, particularly within the African and Asian continents, to allow multicenter licensure trials of candidate vaccines. There is an urgent need for validated preclinical and clinical models to evaluate TB vaccine candidates as it will not be feasible to evaluate all vaccine candidates in large-scale efficacy trials.