The wheels of scientific research move slowly. An investigator might spend decades pursuing a single discovery, enduring countless setbacks, dead ends and course-corrections along the way. Then: a breakthrough! — and science that advances from lab bench to patient bedside, changing the standard of care and affecting millions of lives.

After nearly six years of the kind of measured and often frustrating work that is a hallmark of academic medicine, Styliani Karanika, M.D., and a team of Johns Hopkins researchers including professors Petros Karakousis, M.D., and Richard Markham, M.D., may be on the verge of such a breakthrough, having taken a significant step forward in the fight against tuberculosis (TB) with the development of a promising therapeutic vaccine for TB.

For many, tuberculosis seems like a disease of the past. While it’s true that improvements in medicine and public health have contributed to a better understanding of TB, the complex infection remains a persistent global health concern.

“A misconception that we have is that TB is not a huge issue, so that’s why we don’t need to spend a lot of money [on research],” says Karanika, assistant professor of medicine in the Division of Infectious Diseases at the Johns Hopkins University School of Medicine.

According to the World Health Organization, TB is the world’s deadliest infectious disease, present in every nation and age group. An estimated 10.7 million people contracted TB in 2024; 1.23 million of them died. TB is also the leading cause of death for people living with HIV, and it is a major contributor to antimicrobial resistance, a global public health crisis and a serious threat to health security worldwide. In the United States, the Centers for Disease Control and Prevention reports a steady rise in TB incidence every year from 2020–2024 after nearly three decades of decline, with more than 10,000 cases reported in 2024. Large, active outbreaks of infection occur several times a year across the country.

While TB is preventable and treatable, the infection is also highly adaptable, and the challenges of fighting it are numerous. TB spreads easily in crowded environments, elevating risk in certain high-probability settings like shelters and prisons. Effective treatment for TB can take six months or more, with a combination of antibiotics that often cause side effects so debilitating people choose to stop taking the drugs long before the infection has fully cleared, leading to relapse. Some TB strains are resistant to preferred medicines like isoniazid and rifampicin, which makes treatment harder, longer and more expensive; these drug-resistant strains also add to the growing crisis of antimicrobial resistance. Additional barriers to care include limited access to rapid diagnostics, quality medications, monitoring and follow-up care, and socio-economic factors like poverty and stigma.

The prospect of figuring out how to address these challenges is what drew Karanika to tuberculosis research during her fellowship in infectious diseases at Johns Hopkins.
“When I came to Hopkins, I had no previous experience with TB,” Karanika says. Encouraged by Division of Infectious Diseases leadership to explore different areas of research interest, she says she became fascinated by the concept of host-directed therapies for TB. “Basically, how to manipulate the immune system, how to enhance the immune system to help better control TB … I decided I wanted to take a complete turn.”

The work that would inform the TB vaccine breakthrough began during fellowship, in the fall of 2020. Karanika was in her second year of the program, when focus shifts from clinical training to guided research. Working with mentors Petros Karakousis, M.D., professor of medicine in the Johns Hopkins Division of Infectious Diseases, and Richard Markham, M.D., professor of molecular microbiology and immunology in the Johns Hopkins Bloomberg School of Health, Karanika says she developed a deeper understanding of TB as well as the gaps in knowledge that have made finding an easy, effective cure so elusive.

“There are many difficulties and many unique issues that I was not aware of from the very beginning,” she admits, citing the stringent qualifications required of TB lab workers, lengthy experiments and their extra costs, the necessity of pausing work for weeks or even months at a time to allow for observation and assessment, validating multiple results in many different samples in duplicate or triplicate. One small aspect of the study — evaluating the likelihood of TB relapse after administering the vaccine along with antibiotic treatment — took almost a year to complete.
Karanika says that coordinating complex logistics in a lengthy study is to be expected, and patience is key.

“As I was told, that’s why we call it re-search — because we have to do things again and again,” she quips. “There are many technical aspects [to manage and consider] until we optimize our protocols, until we’re confident about the results we’re going to report.”

Over the next several years, work unfolded methodically through a series of logical next steps pursued with painstaking attention to detail.
Karanika is now focused on expanding the study and improving efficiency through advocacy, collaboration and increased funding. Another crucial component: building a team that can sustain the work through the years to come.

“One thing I learned during this process and all these years is that I don’t really focus anymore on the paper qualifications of a team member,” Karanika explains. “I focus on their personality and their motivation. If somebody is motivated to learn something and to do something, they can do everything. If they’re not motivated, if they’re not passionate about what they’re doing, I don’t think they’re going to like the long road ahead.”