“Elimination of tuberculosis (TB) is more than an aspiration. We know it could become a reality, but this will happen only if we achieve radical transformation in the way TB is diagnosed, treated and prevented. This goal can be realized only if TB research is intensified and envisioned in an entirely new way.” These are the first words of Lucica Ditiu, Executive Secretary of Stop TB Partnership, in the International Roadmap of Tuberculosis Research, launched this weekend in Lille.
The roadmap includes contributions of TBVI's director Jelle Thole and is the product of the Research Movement, created by the Stop TB Partnership and the WHO Stop TB Department in 2006 to address the urgent need for increased commitment for TB research. The Research Movement, led by Christian Lienhardt and of which TBVI a member, is intended to provide leadership and advocacy to mobilize increased resources in support of a coherent and comprehensive global TB research agenda to meet the Stop TB goals and targets; and to provide a forum for TB researchers and funders of TB research to coordinate priorities and actions.
“Research is a fundamental means to maximize the advances already achieved in TB control through strengthening of programmes and health services, and alleviation of risks and determinants,” says Mario Raviglione, director of WHO Stop TB department. “Current tools that are widely used in TB high-burden countries are not the ideal ones to reduce deaths effectively and contain the TB epidemic. Of all four measures promoted, research is the key milestone for any attempt to impact on incidence in a substantive way.”
The overall objective of global TB research roadmap was to define the essential research questions that provide a common framework for scientific disciplines to work concurrently and collaboratively for better TB control towards the elimination of TB.
Research and development of new vaccines
Fundamental research questions for vaccine development include identification of the components of the host immune system that are critical for the control and elimination of TB bacilli. This involves determining the respective roles of innate and adaptive immunity in preventing M. tuberculosis infection and reactivation of latent disease, and better understanding of the immune response to different metabolic stages of the pathogen in various populations (e.g. according to HIV infection status and age, from infancy to adolescence and adulthood).
The key research areas are:
- identification of immunodominant antigens (or their components) that could be added to vaccines to increase protection;
- identification of correlates of protective immunity after vaccination;
- determination of appropriate clinical endpoints and immunological read-outs for vaccine trials (especially in children); and
- identification of novel model systems for preclinical and clinical (challenge model) testing of TB vaccines, including pre- and post-exposure models and models to mimic reactivation.
The main priorities include:
- better understanding of the immune responses to new vaccines and bacillus Calmette-Guérin (BCG), both in animal models and in different human populations and age groups;
- development of improved vaccines for prime–boost vaccination (including improvement of BCG as a prime) and the optimal conditions of use (duration of intervals, boosting dose and number of boosts);
- development of standardized assays to assess vaccine-induced immunogenicity to allow better comparison of candidate vaccines in different settings;
- conduct of prevaccine epidemiological studies to facilitate TB vaccine development and implementation of vaccine trials; and
- identification of suitable methods for standardizing and planning trial sites and protocols.
The questions listed in this document, not only in the area of vaccines, but also in the area of treatment, diagnostics, fundamental research and operational and public health research, are complex. They can be addressed only by close coordination and collaboration among all stakeholders, across disciplines and across settings. This document lists the essential research questions that will provide a common framework for various scientific disciplines to work concurrently and collaboratively towards better TB control and elimination. Responses to these questions are expected to fill knowledge gaps and indicate ways to develop and use new, safe, effective, accessible and affordable tools for the control of TB, so as to best prevent, detect and treat TB in all populations (including those with TB–HIV co-infection or MDR-TB and paediatric populations).
TBVI is ready to take up its responsibility!