The Need for New Vaccines

“One of the historic ironies of tuberculosis research is that it has always been assumed that the current interventions would eliminate this disease as a major public health problem.  BCG, an attenuated bovine tuberculosis strain, was discovered in 1908, and was thought to be the vaccine for tuberculosis. Streptomycin in the 1940s was hailed as the wonder drug for tuberculosis. Yet even with better antibiotics, tuberculosis remains a major global health problem. Concomitant with these historically shortsighted miscalculations were reductions in support for research on new tools and strategies, based on the assumption that with existing interventions the disease would disappear. It has not.”  - Barry Bloom, MD, Harvard University Distinguished Service Professor

The most effective way to stop the global TB epidemic is to prevent the spread of M. tuberculosis. That, however, is increasingly difficult with the rise of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB).  The WHO reports that MDR-TB cases are on the rise in most of the high disease burden countries, and XDR-TB has been identified in 100 countries.  Identifying resistant forms of TB adds another challenge.  In 2013, only 45% of the total estimated MDR-TB cases worldwide were notified. While some high burden countries like India and South Africa have improved their detection rates, nations like China continue to struggle.

Treating our way out of this epidemic is neither possible nor affordable for most countries, given the limitations inherent in the tools used today. The cost of treating MDR-TB is up to 200 times that of treating drug-sensitive TB.  MDR-TB treatment also often requires up to two years of treatment, daily injections and in-patient care. The costs for scaling up and achieving universal access to MDR-TB and XDR-TB treatment and preventive therapy can prove logistically and economically prohibitive.

There is one vaccine, Bacille Calmette-Guérin (BCG), being used today to prevent TB in infants. But even though BCG is the most widely used vaccine in the world, it has not successfully eliminated the disease due to its limited efficacy. Research and development for new vaccines would have the biggest impact on the epidemic, and remains the cornerstone to reaching global elimination within the coming decades.

Global Efforts

The medical and research communities agree that new vaccines are central to future TB elimination programs. Like every other major infectious disease in the history of mankind, prevention through vaccination is expected to be the most cost-effective tool in eradicating and controlling TB. A new model incorporating data from 183 countries demonstrates that a partially efficacious (60 percent) adolescent and adult preventative vaccine, delivered to 20 percent of the target population, could avert as many as 30-50 million new cases of TB by 2050. A significantly improved infant vaccine, over the 90-year-old Bacille Calmette-Guérin (BCG) vaccine, could potentially avert an additional 7-10 million new cases over that same period of time. New TB vaccines would be our single greatest preventative tool in the fight against TB. Without them, TB will not be eradicated.

Since 2005, global investments of more than US $600 million have led to more than 15 TB vaccine candidates being tested in more than 50 human trials. In addition, promising activities for the development of new biomarkers have emerged. Today, the capacity exists for vaccine production to carry out large-scale clinical trials, particularly in disease endemic countries. There is also broad support for research within the communities where clinical trials are being conducted. For the first time in decades, basic information on safety and immune responses to a variety of first-generation TB vaccine candidates is available. The effectiveness of these vaccine candidates to prevent TB will be revealed over the next decade, and plans for regulatory approval and delivery of effective vaccines are being established.

The next phase of vaccine development will prove to be the most crucial. Limited resources - both financial and clinical - demand a structured and transparent “rational selection” process for advancing the most promising TB vaccine candidates. This cannot be the work of a single foundation or a small set of governments or biotech partners, but must involve the larger global public and private community.

Challenges

Despite more than a decade of progress, including several TB vaccine candidates entering clinical trials, there are still scientific challenges facing the TB vaccine field:

  • A lack of understanding of how vaccines work or the protective immunity against TB in different age groups and populations
  • No correlate or surrogate endpoint of protective immunity, meaning new TB vaccines cannot easily be evaluated in experimental animal models or in early clinical trials
  • The current need to evaluate vaccine efficacy in long, protracted and costly clinical trials
  • Large gaps in our understanding of TB, the way our natural immune system responds to TB infection, and antigen identification and selection

Aeras and our partners have established working groups on several of these topics in order to find answers that will bring us closer to developing an effective TB vaccine for the world.

Cost of a New Vaccine

The estimated cost of advancing the TB vaccine portfolio within the next 10 to 15 years is less than US $1 billion. These costs assume that the field is applying rigorous selection criteria and innovative trial designs to facilitate the down-selection of candidates, thus preserving scarce resources to advance only the most promising candidates into more expensive, later stage trials. Considering the cost of TB treatment strategies, the relative cost to develop new TB vaccines is nominal given the massive potential.