Key issues in the clinical development and implementation of TB vaccines in South Africa.

Abstract

Significant progress has been made in advancing the development pipeline for a new and more effective

TB vaccine with some candidate vaccines now in late stage clinical evaluation. However, progress has

been hampered by an incomplete understanding of the components of a protective immune response

and limited animal models, rendering the field unable to reliably predict vaccine efficacy earlier in

preclinical development, including by evaluation in animal models, and limiting the predictive utility of

comparing immunogenic effects across vaccine candidates in phase I/II studies. Consequently, new

candidate vaccines have to be evaluated for efficacy in large-scale phase II/III trials using clinical

endpoints. Apart from the technical challenges of characterising TB incidence in target populations at

high risk of acquiring TB disease and standardising case definitions in order to improve both the

sensitivity and more importantly the specificity of trial endpoints, there is an urgency in expanding and

supporting the considerable trial infrastructure that will be required to evaluate and ultimately license

a new TB vaccine. In the longer term, implementation strategies are dependent on what policy makers

most value. Economic analyses will be essential to guide policy and implementation. This paper outlines

the gaps and challenges and identifies solutions for effectively developing and efficiently introducing

a new TB vaccine.