By Mark Feinberg, M.D., Ph.D., President and CEO of IAVI
The urgent need for more widely effective tuberculosis (TB) vaccines isn’t new. TB, a centuries-old pulmonary disease caused by infection with Mycobacterium tuberculosis, is the world’s deadliest infectious disease and one of the top 10 leading causes of all deaths worldwide. What is new is that the prospects for developing improved TB vaccines are now more promising than ever.
Results from a Phase IIb study involving more than 3,500 adult volunteers from Kenya, South Africa, and Zambia showed that the GSK investigational TB vaccine candidate known as M72, administered along with the company’s AS01E adjuvant, was 54 percent effective at preventing active pulmonary TB disease in adults (DOI: 10.1056/NEJMoa1803484).
Additional promising data emerged from a Phase II trial evaluating revaccination with the only licensed TB vaccine, known as BCG (bacille Calmette-Guérin). This vaccine, developed nearly 100 years ago, is administered routinely to infants in high-incidence settings to protect against the development of TB disease. But protection rates with the BCG vaccine vary widely, the precise duration of protection is unknown, and because this vaccine does not protect against initial TB infection or reactivation of latent TB infection, the bacteria still spreads and TB disease still develops at an alarmingly high rate. In 2017, there were 10 million new cases of TB disease reported, according to the World Health Organization to the World Health Organization (WHO). However, results from this recent clinical trial offer new hope for how the BCG vaccine could be used. This study showed that revaccinating South African adolescents with the same BCG vaccine they received as infants was 45 percent effective in preventing sustained TB infection (N. Engl. J. Med. 2018; 379:138-149).
Data from these clinical trials are changing the way we think about TB vaccine development. These results provide the opportunity to identify the basis of vaccine-elicited, protective immune responses. The question is no longer whether it is possible to develop new TB vaccines, but how to expedite development of the candidates or approaches that look promising, and also how to utilize emerging immunologic insights to hasten the design and development of even better ones.
This comes at a time when the attention being given to the urgent need for improved ways to treat and prevent TB is at an all-time high. For the first time, the United Nations (U.N.) General Assembly held a high-level meeting focused on accelerating efforts to end TB.
The combination of scientific advances and increased political attention suggest that this is a pivotal moment in the decades-long quest to develop more widely effective TB vaccines. It is a pivotal moment for IAVI as well. More than 20 years after IAVI was created to ensure the development and global availability of an HIV vaccine, the organization is broadening the scope of its activities. IAVI is extending its scientific capabilities, clinical research capacity, and vaccine and monoclonal antibody technology platforms, working in partnership with others, to facilitate the development of approaches to prevent and treat additional diseases that are of major public health concern. TB is one of these diseases. A capable and dedicated clinical research team in South Africa from Aeras — a product development partnership focused on TB vaccine development — will join IAVI and its African clinical research center partners to build upon the recent clinical trial results and accelerate the development of promising vaccine candidates. The Aeras team played an essential role in both the GSK M72 and the BCG revaccination trials (conducted in collaboration with Sanofi). We are excited to welcome them to IAVI and to support the broader efforts to advance TB vaccine development at this critical juncture.
IAVI’s involvement in TB vaccine development will only strengthen our ability to catalyze new partnerships and contribute to the development, testing, and delivery of an eventual HIV vaccine, as well as vaccines against other diseases of global importance.
HIV and TB are already inextricably linked, with incredibly deadly consequences. TB is the top killer of people living with HIV/AIDS, and those infected with HIV accounted for nearly 20 percent of the 1.6 million TB deaths reported in 2017, according to WHO estimates. In some of the hardest-hit regions of the world, HIV has fueled the spread of TB.
If we want to do everything we can to minimize the death toll from AIDS, we must address TB. And there is no better time to contribute to this effort than now.