While IDRI’s novel tuberculosis vaccine candidate, ID93+GLA-SE, continues to move forward in a Phase 2a trial in South Africa, IDRI scientists are turning their sights to a host-directed approach for combatting TB. In order to defeat this devastating infectious disease that kills upwards of 1.5 million people each year, IDRI scientists are focusing on multiple approaches to treat and prevent TB.

With a $6.8 million grant funded by the National Institutes of Health (NIH), a team of IDRI scientists propose to use IDRI’s unique adjuvant platform to manipulate the body’s response to Mycobacterium tuberculosis (Mtb), the bacterium that causes tuberculosis, rather than targeting the bacteria themselves, a concept called host-directed therapy. IDRI’s adjuvants activate macrophages – the white blood cells of the immune system that patrol the body, engulfing and destroying pathogens such as Mtb while presenting its’ antigens and activating other immune cells.

“Our goal is to boost host immune responses and treat TB rapidly by developing a candidate therapeutic product that offers significant potential for the treatment of drug resistant TB,” said Rhea Coler, Ph.D., Sr. Vice President of Preclinical & Translational Research for IDRI, who, along with Sue Baldwin, Ph.D., serves as a co-principal investigator on the grant. “We hope to treat people with active TB or use this as a vaccine to prevent tuberculosis.”

Photo from Africa.
Tuberculosis presents one of the world’s biggest health challenges, particularly in South Africa, where IDRI’s TB vaccine is currently in clinical trials.

The combination of chemical compounds, being screened through IDRI’s TB Discovery Program, led by Tanya Parish Ph.D., Vice President of Drug Discovery as potential drug targets, with IDRI adjuvants creates a different way of combatting Mtb. “The very nature of adjuvants is to boost an immune response,” explained Coler. “In this case, the adjuvants ensure that host cells have more power to fight the growth of Mtb.”

Early screening studies show promising results: with adjuvant treatment some bacteria are stunted, while others are dying. “We are continuing our studies using IDRI’s new host/pathogen capacity for high content analysis (HCA) under Biosafety Level-3 conditions (the lab level needed to safely and effectively test highly infectious organizations like the bacterium that causes TB),” said Coler.

Meanwhile, IDRI continues moving forward with its novel tuberculosis vaccine candidate, ID93+GLA-SE, which has shown prophylactic and therapeutic efficacy in preclinical studies. Phase 1 studies yielded promising safety and immunogenicity results in uninfected adults in the U.S. and in Mtb-infected and uninfected adults in South Africa. “Our Phase 2a trial, funded by the Wellcome Trust, is evaluating ID93+GLA-SE for safety, dose selection, and immunogenicity in cured TB patients following a standard course of chemotherapy in South Africa. This is in preparation for a planned Phase 2b trial that will evaluate the selected dose for efficacy in the prevention of recurrence of TB disease in cured TB patients.” Recurrence is a key problem: it is estimated that retreatment of patients with recurrent disease accounts for nearly half of MDR-TB cases.