The elusive TB vaccine

Humans and Mycobacterium tuberculosis (Mtb)—the microorganism that causes tuberculosis (TB)—have co-evolved for thousands of years. Mtb manages to avoid and exploit different cells of the human immune system, making it a particularly-effective disease-causing agent. TB is a treatable disease, but the long duration of pharmacotherapy—at least six months—has raised hopes that a vaccine can prevent the disease altogether.

Actually, there’s an existing anti-TB vaccine called Bacillle Calmette-Guerin (BCG). But while it is part of many country’s immunization programs, it offers limited protection from TB beyond childhood. Despite the public health significance of a disease that kills over 1.6 million people annually, there are multiple reasons why we don’t have an effective vaccine for it yet.

Firstly, global health leaders did not feel the need for a vaccine, thinking that TB would be eradicated with methods like case detection and antibiotic treatment that have proved very successful in Europe and North America. Only in the late ’90s, when the World Health Organization declared TB a “global emergency” in the wake of its persistence and resurgence, was TB vaccine research and development vigorously pursued.

Secondly, the very nature of TB makes it a hard target for vaccination: The infection can stay in the body without causing any disease (“latent TB”)—only to (re)activate years or even decades later. Simply put, this means that a TB vaccine must be capable of generating very long-lasting immunity or be suitable for repeated boosting.

Thirdly, because TB is caused by a slow-growing organism, animal vaccine experiments take a long time—six months or a year for just one round—and cost a lot of money. Scientists use mouse, guinea pig and rabbit models to test vaccine safety and efficacy, but none of them perfectly simulates human disease (and response). The macaque model is much better, but prohibitive in terms of cost and logistics.

Lastly, we still lack the technology to measure the degree of protection conferred by an experimental vaccine. Instead, every vaccine has to be evaluated through extensive testing to see if it can reduce disease or death. This difficulty in evaluation further increases the time and resources required to test a new vaccine.

Still, there are reasons to be optimistic. The Collaboration for TB Vaccine Discovery, an initiative of the Bill & Melinda Gates Foundation, has made significant progress in standardizing experimental design and aligning endpoints of TB studies. Researchers at the University of Bath are working on a new TB vaccine that can be protected from heat damage, while those from the University of Zaragoza in Spain are developing a vaccine called
MTBVAC that early tests suggest is more effective than BCG. Also very recently,
scientists from the University of Sydney have shown promising results from animal studies of an inhaled vaccine.

One way to contribute to these positive developments is to continue calling attention to the largely-overlooked TB pandemic. Although it remains one of the top causes of death worldwide, it receives little coverage in part because it is a slow, undramatic disease—and that it has been around for so long.

Another response is to strengthen national immunization programs in general. Of what use is a vaccine if people won’t take it? In this age of fake news, antivaccination movements and medical populism, it is important for government and non-government organizations to (re)build trust among the public to ensure that any vaccine will actually be accepted. Toward this end, many countries need to improve their communications strategies and community engagement.

Finally, there is a need for political leadership to support TB research, strengthen existing treatment protocols and address the social determinants of a disease that mostly (but not exclusively) impacts the poor
and the marginalized. Vaccines may hold promise in the future, but there are existing steps that we can take to stop TB now.

Melvin Sanicas (@Vaccinologist) is a public health physician specializing in vaccines and infectious diseases. Gideon Lasco (@gideonlasco) is a medical anthropologist and Philippine Daily Inquirer columnist.