The research of Samuel Vidal, MD, PhD, targets one of the biggest public health challenges in the world, tuberculosis (TB), which affects as many as a quarter of the world’s population. An improved vaccine for TB could help save millions of lives, but decades of attempts have failed to prove fruitful.

Vidal hopes his approach will be different. Initially inspired as an undergraduate by the advent of the first effective antiviral drugs to treat the AIDS virus, he was later schooled unexpectedly in real-time vaccine development during the COVID-19 pandemic. Now he’s applying what he learned from both to overcome the barriers to creating an improved TB vaccine. A Harvard Catalyst K12 award has supported this effort.

Vidal is an instructor in medicine at Harvard Medical School, an associate physician at Brigham and Women’s Hospital, and a staff scientist in the Barouch laboratory at Beth Israel Deaconess Medical Center. We caught up with him as he had just completed a K08 application seeking his first NIH grant.

Scientists have been trying to develop a TB vaccine for 100 years or so. What draws you to take on this problem?

As a group, infectious diseases are among the leading causes of illness and death worldwide. Within infectious diseases, some of the most impactful pathogens on global health include TB, HIV, and malaria, among others. Historically many of these diseases, including TB, have been underfunded and understudied, and so much remains to be learned.

One scientific challenge the field is facing is determining which antigens to focus on. Why has that been a stumbling block in TB research?

The biology of TB is complex and fascinating, and one reason is that TB has a large genome. By comparison, the SARS-CoV-2 genome has about two dozen genes, and it was clear early on to vaccine developers that the spike gene was an important target for vaccines. That proved to be very important for the rapid development of vaccines during the pandemic.

The picture with TB is different. Instead of a few dozen genes like SARS-CoV-2 and many other viruses, the TB genome contains approximately 4,000 genes. So the question of which antigens to select for an effective vaccine is scientifically very challenging. The field has been wrestling with this challenge for decades and the answer is still not fully understood.

The goal of our project was to study as many of these antigens as possible and compare them head to head. We wanted to explore whether using a systematic, large-scale strategy could give insights about what potentially may be the best subset of antigens for a vaccine.

How does this award advance your research trajectory as an early-career investigator?

We used the K12 grant to perform studies that yielded the preliminary data for follow-up K08 and Centers for AIDS Research (CFAR) applications. So the K12 fulfilled a critical “bridging” function by both moving our science forward, while at the same time helping to advance my career development by submitting additional grant applications.

So the K12 fulfilled a critical “bridging” function by both moving our science forward, while at the same time helping to advance my career development by submitting additional grant applications.

For example, as part of my K12 project, we had set up a collaboration with a clinical trials network to obtain valuable clinical samples from individuals with prior exposure to TB. We were able to perform the experiments that we had proposed in the K12 application, and those results became preliminary data for my subsequent grant applications.

What appeals to you about the path of a physician-scientist?

I try to convey to the trainees I mentor that there are as many paths in medicine and science as there are trainees, and all of those paths can be important. Important discoveries are made by those who are purely clinical researchers as well as by basic science researchers. The physician-scientist path is somewhere in the middle, straddling both the clinical and research settings.

Something else I try to convey to trainees is how important mentors are in career development, especially for those at early stages. I became interested in the physician-scientist path in college, when I took an advanced chemistry course on the development of antiretroviral drugs for HIV. One of my mentors as an undergraduate was chemistry professor Fran Blaise, who was passionate about teaching us how these lifesaving drugs were developed. That was a very exciting moment for me that crystallized how science could be used in the service of human health.

The physician-scientist path is long, including eight years of school before residency and fellowships. It’s learning medicine and science. But at the same time, it’s rewarding and fascinating to both treat patients and make discoveries in the lab.

The physician-scientist path is long, including eight years of school before residency and fellowships. It’s learning medicine and science. But at the same time, it’s rewarding and fascinating to both treat patients and make discoveries in the lab.

What has the K12 award meant to you?

I cannot speak highly enough of the Harvard Catalyst K12 program. It’s a wonderful program for young translational investigators that serves as a springboard into an NIH-funded academic career in multiple ways.

K12 awardees are enrolled in the Harvard Catalyst GRASP program, which is specifically designed for junior academic investigators to learn how to conceptualize and develop a strong NIH grant proposal. In addition, we have frequent meetings with the K12 Principal Investigator Karen Miller, MD, who provides mentorship, either personally or with additional speakers, as well as advice and guidance about how to prepare for a career as an NIH-funded academic researcher.

Another important role for the K12 is to serve as bridge funding during a window of time when trainees are working diligently in the lab to perform impactful science, but it may take several years to publish a manuscript and be a strong candidate for NIH grants.

The K12 fills that critical gap and helps the transition from training to independence. For example, TB is a very slow growing bacterium, and vaccine experiments can take up to six months to complete. Because of this slow biological pace, completing an impactful research project can take several years of diligent work. During that time it can be challenging to sustain oneself with grant funding in the academic environment.