International Roadmap for TB outlines challenges in TB fight

In the recently published International Roadmap for TB, three TB experts recently discussed the progress that has been made in TB vaccine research and the challenges that remain in fully realizing a blueprint for vaccine research and development.

According to Christian Lienhardt, the senior scientific advisor for the Stop TB Partnership, Uli Fruth, a scientist with the Initiative for Vaccine Research, and Michel Greco, the chair of the Working Group on New Vaccines, there are multiple challenges that must be addressed to develop novel and better TB vaccine candidates.

The challenges include spreading the knowledge of how protective immunity in TB works and what the best vaccine antigens are, determining the most effective delivery methods and the most appropriate vaccination strategies, expanding the infrastructure and capacity to conduct large-scale trials in endemic countries, the development of standardized immunological assays for better vaccine candidate comparison and creating well-controlled and large epidemiological cohort studies in adolescents and infants to provide baseline TB incidence data, and to ascertain whether or not large-scale efficacy trials are suitable. Additionally, other difficult hurdles remain for new TB vaccines.

"In addition, and in order to ensure an ample supply of quality candidate vaccines for clinical trials and minimize the lag time between licensure and worldwide distribution, it is imperative to invest in vaccine manufacturing capacity," the authors said. "Lastly, appropriate delivery, regulatory and access strategies for TB vaccines, including the development of effective regulatory pathways that shorten review timelines without compromising the ultimate quality of vaccines will have to be developed and implemented."

According to the authors, multiple groundbreaking initiatives have occurred in the last two years to address the many challenges TB vaccination development has faced. The Global Plan to Stop TB 2006-2015 received a major revision in 2010 to emphasize research and development. The research and development goals for the plan now anticipate that by 2015, there will be four new TB vaccine candidates entering Phase III clinical trials for efficacy and safety, that appropriate infrastructure and capacity will be in place, and that regulatory pathways and delivery/access strategies will be created to minimize lag time between the licensure and distribution of new vaccines.

The International Roadmap for TB research has also identified important research priorities relating to TB vaccines, including placing a high priority on the development of improved vaccines for prime-boost vaccination strategies. This includes the improvement of the BCG vaccine and determining the optimal conditions of use including the boosting dose, the number of boosts and the duration of intervals.

The Blueprint for TB Vaccine Development, which was developed by the Working Group on New Vaccines of the Stop TB Partnership logically continues and expands the two initiatives. The blueprint provides in-depth overviews of the needed scientific steps and addresses regulatory strategies and well thought-through pathways of policy.

"The Blueprint for TB Vaccines provides a much needed coordinated plan for rational vaccine development," the authors said. "Buy-in by relevant stakeholders will be crucial to translate it into intensified collaboration between vaccine developers, increased involvement of the private sector, enhanced coordination among funders and timely dialogue with future users. If this can all be achieved, the blueprint will represent a key milestone to ensure the development and uptake of new TB vaccines and vaccination strategies as key components of a global strategy towards a world free of TB."