The Tuberculosis Vaccine Pipeline
with TB antigen 85A. The first infant received a dose in July 2009 as part of a phase IIb proof-of-concept study. This is the first time in over 80 years that a vaccine has been tested for efficacy in infants (Beresford and Sadoff 2010). The trial is comparing MVA85A versus placebo in BCG-vaccinated, HIV-negative infants. The first results are expected in 2012 (McShane 2010). Mycobacterium vaccae is a mycobacterium which has been evaluated as an immunotherapeutic vaccine for people with TB infection. In the 2009 pipeline report, it was reported that Aeras’s external Vaccine Selection Advisory Committee had reviewed the data from the Dar Dar study—a trial that evaluated M. vaccae in HIV-positive adults who had been vaccinated with BCG—and recommended that Aeras determine if new M. vaccae vaccine could be manufactured since the trial depleted the existing supply. Aeras has undertaken some limited process-development work to produce more vaccine and this work is almost complete. At this time Aeras does not have any immediate plans for further involvement (Willingham 2010). The limited data on M. vaccae are uninspiring. A 2003 Cochrane Review review concluded that M. vaccae provided no immunotherapeutic benefit for people with TB and therefore that no further trials were warranted (de Bruyn 2003). However, evidence from the Dar Dar study has suggested that a multidose M. vaccae vaccination was associated with protection against TB disease in people with HIV with CD4 counts above 200 (von Reyn 2010). The Dar Dar study results would need to be confirmed via additional studies before any conclusions could be made about effectiveness (Kaufmann 2010). M. vaccae is the only vaccine candidate to make it to phase III, but it appears that there is neither supply of the construct nor any research institution evaluating it at this time.
What Is Needed? There are still many unanswered questions about the TB life cycle, the spectrum of TB infection and disease, and the impact of host genetics on the immune response that hamper vaccine development. More attention and resources need to be focused on basic scientific research. This is critical to keeping the pipeline full of new candidates, improving existing prevention tools, and identifying novel strategies to induce safe and durable immunity to TB infection and disease. A clear understanding of the differing characteristics of TB in its latent and disease state could lead to the development of a vaccine construct that could prevent infection and thereby significantly lower future cases of TB disease. The identification and validation of correlates of immunity will be vital to expediting the evaluation of any new vaccine candidate. Without the ability to predict whether a vaccine is able to induce an adequate protective immune response and to measure the quality of that response, massive resources—which are not currently available—will need to be dedicated to conducting long-term, large145