BIDMC Investigators Pave the Way for Next-Generation TB Vaccine

Investigational mRNA Vaccine Protected Mice Better Than the Century-Old Vaccine — Limiting Infection and Slowing Disease Spread

Tuberculosis or TB, an airborne bacterial respiratory infection, is one of humanity’s oldest foes and is today the world’s leading cause of death from infectious disease, claiming more than 1.2 million lives each year. The single available vaccine protects young children from severe cases of TB but does little to prevent the spread of disease in adolescents and adults.  

Now, scientists at Beth Israel Deaconess Medical Center (BIDMC) have created a new TB vaccine candidate with newly identified antigens and delivered by mRNA technology, the same approach that allowed the rapid development of safe and effective vaccines against COVID-19. As the team reported in Cell, the next-generation TB vaccine concept is planned for clinical testing in adults and could result in an important advance in TB prevention that could benefit all age groups. 

“We systematically evaluated multiple potential TB vaccine antigens to develop a novel TB vaccine candidate,” said corresponding author Dan H. Barouch, MD, PhD, director of the Center for Virology and Vaccine Research at BIDMC, whose work contributed to the development of Johnson & Johnson’s  COVID-19 vaccine. “We used the mRNA platform that is flexible, scalable, and can combine multiple antigens into one shot.”

TB lacks an obvious target for vaccine design. Using a dataset of immune responses in humans exposed to TB, Barouch and colleagues developed a screening pipeline to test which antigens elicited responses from human immune cells, then ranked them by strength. The process revealed a multitude of TB antigens for potential use in a vaccine. Selecting the top contenders in each of several categories, Barouch and colleagues designed a vaccine concept that combined three TB antigens—called a trivalent vaccine—and tested it in an animal model. 

“Choosing which antigens to target is a significant challenge in TB vaccine development,” said lead author Samuel J. Vidal, MD, PhD, a staff scientist in the Barouch Laboratory at CVVR.  “The three antigens we chose have not previously been evaluated in clinical trials. Our trivalent mRNA vaccine concept improved upon the century-old BCG shot in animal models—it reduced infection rates, reduced bacterial spread, and lowered bacterial levels in the lungs.” 

The trivalent vaccine antigens also triggered immune responses in humans exposed to TB, suggesting that the approach could work in people. The vaccine concept is now planned to move into Phase 1 clinical trials, the first step in testing its safety and effectiveness in humans, offering a potential path toward better protection against one of the world’s most devious infectious diseases.

“Taken together, our findings open the door to a new vaccine candidate for TB,” said Barouch, who is also is also a professor of medicine at Harvard Medical School and a member of the Ragon Institute of MGH, MIT and Harvard. “We’re excited to be moving this novel TB vaccine candidate toward clinical trials.”

Coauthors included Ninaad Lasrado, Lisa H. Tostanoski, Jayeshbhai Chaudhari, Esther R. Mbiwan, Ganad D. Neka, Ellis A. Strutton, Alejandro A. Espinosa Perez, Daniel Sellers, Julia Barrett, Michelle Lifton, Erica N. Borducchi, and Malika Aid of BIDMC; Shoko Wakabayashi of Harvard T.H. Chan School of Public Health; Behnaz Eshaghi, Ana Jaklenec, and Robert Langer of Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology; Wenjun Li of University of Massachusetts Lowell; and Thomas J. Scriba of University of Cape Town.

Funding: Gates Foundation INV-050234, National Institute of Allergy and Infectious Diseases 5T32AI007387, National Center for Advancing Translational Sciences 5K12TR004381, and philanthropic sources.

Vidal and Barouch are co-inventors on US Patent application no. 63/610,211 describing the novel TB vaccine antigens. For a complete list of disclosures, please see the publication.