Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis, a highly transmissible species of bacteria that spreads easily through the air.

Although TB is classified as a curable and preventable disease, it remains a major global health concern. In fact, the World Health Organization reports that more than a million people die from TB infection each year, making it the second-most deadly infectious disease on the planet, behind only COVID-19.

Researchers at McMaster University have been studying TB for decades. Their work, based largely out of the Michael G. DeGroote Institute for Infectious Disease Research (IIDR), has advanced the global understanding of TB and pushed forward next-generation designs for TB immunization strategies.

Taking on “the deadly duo”

In Amy Gillgrass’ IIDR lab, researchers are working tirelessly to develop new therapeutics and vaccines to improve TB patient outcomes.

But Gillgrass’ sights aren’t set on tackling TB alone: She’s interested in how M. tuberculosis and human immunodeficiency virus (HIV) — together known as “the deadly duo” — combine to cause fatal co-infections.

A significant overlap in high incidence areas of HIV and TB has led to a high prevalence of HIV/TB co-infection, she explains.

For instance, in certain parts of Africa, 60 per cent of all TB patients are also infected with HIV. She also notes that TB is the leading cause of death among people with HIV.

“Co-infections worsen overall disease course, complicate diagnosis, and reduce effective treatment options for both pathogens,” says Gillgrass, an assistant professor in the department of Medicine in the Faculty of Health Sciences.

But studying this specific co-infection is complicated, because such research is typically conducted on small animal models. Since HIV can only infect human immune cells and TB in animals can lack key features of the human disease, standard laboratory animals are not sufficient for Gillgrass Lab research.

To circumvent this, they are studying HIV/TB co-infection in next-generation “humanized mice,” which are immunocompromised mice reconstituted with human stem cells so they develop a human immune system.

“This next-generation mouse model is the perfect translational bridge for investigating human immune mechanisms behind this particular co-infection,” says Gillgrass.

While the COVID-19 pandemic was a major setback for global progress against TB, Gillgrass remains hopeful that the disease will be more manageable in the future.

On top of the important work underway at McMaster, she mentions a recently approved shortened course of antimicrobial therapy for TB as a reason for optimism, noting it should increase treatment compliance, decrease antimicrobial resistance, and reduce overall transmission.

There are several new drug candidates and vaccines in clinical trials that, if approved, will help combat resistant strains of M. tuberculosis, Gillgrass notes.

How TB research laid groundwork for COVID-19 vaccines

Zhou Xing, a professor in the department of Medicine, has been studying M. tuberculosis at McMaster for 25 years.

Xing is fascinated by how this particular species of bacteria can so successfully establish survival niches in the human body without being eliminated by the immune system — something experts call “latent tuberculosis.”

M. tuberculosis is so good at survival, in fact, that, according to the World Health Organization, a quarter of the global population has been infected by the bacteria, though only a relatively small portion will ever actually develop TB disease.

Xing has been investigating immunization strategies against TB to ensure that small portion stays small — and perhaps someday falls to zero.

In collaboration with clinical infectious disease specialists, respirologists, and chemical engineers, his lab has been developing and testing novel tuberculosis vaccine strategies, including those administered by inhalation.

Importantly, Xing says this large body of work was crucial to the rapid development of McMaster’s inhaled COVID-19 vaccines, which are now entering human trials.

“Through our TB vaccine program, we established a robust bench-to-human translational vaccine pipeline here at McMaster,” he says. “This allowed us to pivot and face the new challenge presented by COVID-19.”

Xing says that while the ongoing development of inhaled COVID-19 vaccines has commanded his lab’s recent attention, he remains optimistic that a next-generation TB vaccine will make its way into clinical trials in the future.

Right now, the mucosal TB vaccine that his group developed is being tested in humanized mice by the Gillgrass Lab — studies that may eventually spur clinical translation.