CNS: Call for prioritising TB vaccine research

Tuberculosis, which takes approximately 1.3 million lives per year, imposes not only a huge cost to humanity, but also affects economies worldwide, and not only in developing countries. According to very conservative calculations, the direct costs of TB in the European Union add up to about € 537 million per year. With the threatening rise of Multi-Drug Resistant (MDR) TB and Extensively Drug-Resistant (XDR) TB in the whole world, it is likely that these costs will increase in the near future. Several WHO studies indicate that the disease cannot be eliminated without new vaccines.

TuBerculosis Vaccine Initiative (TBVI)'s annual report, released recently announces that scarce global funding for the development of new TB vaccines forces to select rigorously in the current portfolio of TB vaccine candidates. Because it is not possible to support all vaccine candidates, TBVI developed the instrument of portfolio management to make the right decisions in order to advance vaccine development.

In the past years, dozens of vaccine candidates have been developed in laboratories and more are currently being developed. Many of them are about to enter, or have already entered the preclinical stages of development, which are very expensive and for which only limited funding is available. Therefore TBVI introduced the method of portfolio management: a very efficient and effective method of advancing a vaccine through the pipeline. It is a quality decision-making process that seeks to maximise probability of success against acceptable cost and risk. Together with over 50 research partners, it is working on the development of several types of new TB vaccines and biomarkers (indicators used to monitor the efficacy of new vaccines). Vaccines are needed to protect children, adolescents and adults from getting ill from TB, and we need therapeutic vaccines which are able to shorten the long and burdensome treatment of patients, especially those with MDR-TB and XDR-TB.

The development of a well-balanced and diversified portfolio is a process which builds from a continuous flow of good scientific concepts, molecules or candidate vaccines into a decision-making process. The big challenges facing TB vaccine development are insufficient understanding of protective immune mechanisms, the lack of correlates of protection, and the poor predictive value of animal models. Several candidate vaccines in the current TB vaccine portfolio are based on the concept of critical antigens and desirable immune responses. TBVI wants to diversify the current portfolio by acquiring vaccines with novel effector mechanisms, so as to increase the chance of success.

According to Jelle Thole, Executive Director of TBVI, this approach involves the use of priority setting and entry criteria to select the most promising candidates and to allow entry to new vaccine candidates so as to diversify the portfolio. “Priority setting aims to select the best candidate(s) for further development and down select others that seem less promising. The main criteria being used for comparison are technical feasibility, timelines of development, access conditions, projected health impact, commercial risks and prospects of the candidate. But ensuring that new promising candidates gain admission to the portfolio is essential as well”.

TVBI’s current TB vaccine inventory is composed of a diversity of neonatal priming and adolescent boosting candidate vaccines categorised as being in the Discovery (before Gate 1), Preclinical (past Gate 1), Phase I/IIa (past Gate 2) and Phase IIb (past Gate 3) stages of development.

It is currently managing and coordinating the subsequent NEWTBVAC project (2010-2014) which is supported by the EC FP7 programme and includes 36 research partners. Combined with smaller projects in the same field, funded by the Bill and Melinda Gates Foundation and the Calouste Gulbenkian Foundation, the projects resulted inter alia in: