Houston Methodist scientists, collaborating with Purdue University counterparts, have developed a promising new TB vaccine strategy, a much needed development in the fight against the world's most consistently lethal infectious disease.

In research involving mice, the team's vaccine produced excellent immune protection against tuberculosis, a disease for which there has been no new vaccine in more than 100 years. The new vaccine, delivered nasally, activates dendritic cells and macrophages and enlists T cells to prevent the bacterium from spreading in the lungs.

"It's hard to appreciate the magnitude of the TB problem," says Chinnaswamy Jagannath, a professor of pathology and genomic medicine in the Research Institute at Houston Methodist. "That's why we're excited about this new vaccine strategy. We think it presents new hope against the continued spread of the disease."

While it took less than a year to develop and test vaccines for COVID-19, a new vaccine for TB has proved more challenging, likely because the bacterium contains thousands of proteins — unlike coronaviruses' one main protein — and is well adapted to infecting and hiding inside cells.

Jagannath says a TB vaccine has been as tough to develop as one for HIV-AIDS, whose resistance to countless efforts has been the subject of well-documented frustration in the field. TB has flummoxed researchers for even longer.

A successor to century-old BCG vaccine?

The only current licensed vaccine for TB is the Bacillus Calmette-Guérin (BCG) vaccine, which provides moderate protection against severe forms in infants and young children (not adults), either before or after exposure to TB.

BCG, first given to an infant in a Parisian hospital on July 18,1921, helped wipe out TB in the developed world some 80 years ago, but has failed to stem the tide in the developing world. More than 1 billion people have died from TB the past two centuries, including 1.5 million just last year, roughly the same amount as from COVID-19. About 10 million people get the disease each year.

In July, the World Health Organization called for increased and sustained investments in TB vaccine development, saying "it's time to end the century-long wait."

Jagannath has worked in the field for more than 40 years, initially publishing on treating multi-drug resistant TB, then pioneering new generation autophagy-inducing vaccines targeting the bacterium. Such vaccines work by coaxing the body into cleaning out damaged organelles.

In a 2019 paper in Nature Medicine and subsequently in NPJ Vaccines, Jagannath's team showed its autophagy-vaccine can boost the efficacy of BCG, whose effectiveness is limited because its antigen is sequestered inside a cell. The Houston Methodist team's vaccine releases and digests TB antigens more effectively inside the cells.

In an August paper in Cell Reports Medicine, Jagannath and his team describe the vaccine's unique approach. That includes the use of a peptide — C5 — that is contained in Mycobacterium tuberculosis and that induces autophagy.

The vaccine's intranasal delivery also means it should provide better protection against pulmonary TB infection. BCG protects mainly against extrapulmonary TB in infants.

A vast market and a model for other vaccines

Houston Methodist collaborated with Purdue University professor Suresh Mittal on the project. Mittal's Purdue team provided a bovine-based vector to deliver the vaccine.

Jagannath says the team is hopeful the approach, if born out in future trials, could also be used to make vaccines for HIV-AIDS and cancer.

The potential market for a new TB vaccine is vast — as many as 50 million doses a year. The Houston Methodist-Purdue team's candidate can be given whether or not the person already has received the BCG vaccine.

The Houston Methodist team is currently waiting on grant funding, always a challenge because TB affects the poorest parts of the world, where there is little profit to be made.

Next up for Jagannath's team is a non-human primate trial. If successful, says Jagannath, they hope to move into clinical trials within the next few years.