The Access to Advanced Health Institute (AAHI) published results of a Phase 1 clinical trial demonstrating the safety and immune responses in a new vaccine against tuberculosis (TB), the world’s second deadliest infectious disease (NCT03722472). AAHI’s TB vaccine combines several proteins from Mycobacterium tuberculosis (Mtb), the bacterium that causes TB, into a fusion protein (“ID93”) with a proprietary immune-stimulating adjuvant (“GLA-SE”) in a freeze-dried formulation that can be stored at elevated temperatures (nearly 100 degrees Fahrenheit) for months. The novel single-vial presentation of this freeze-dried TB vaccine candidate elicited a stronger immune response than administration of the same vaccine using separate vials of antigen and liquid adjuvant formulation. AAHI’s single-vial TB vaccine candidate represents significant progress in global efforts to combat TB.
The trial evaluated the safety, tolerability, and immunogenicity of AAHI’s thermostable, freeze-dried single-vial ID93 + GLA-SE vaccine candidate compared to the previous iteration of the vaccine—a two-vial presentation that had demonstrated promising safety and immunogenicity in Phase 2 clinical testing. Importantly, the thermostable single-vial presentation induced higher levels of antibodies than the two-vial presentation, while retaining the vaccine candidate’s ability to activate “helper T cells” that recruit additional immune cells for a stronger immune response. The trial enrolled 48 participants who were to receive two vaccine doses administered intramuscularly 56 days apart, after which the researchers observed the cellular immune response profile thought to be favorable for protection against Mtb.
“Adjuvanted subunit vaccines have re-energized the field of TB vaccine development. This study represents the first temperature-stable adjuvant-containing subunit TB vaccine candidate to be evaluated in the clinic,” says Christopher Fox, PhD, Senior Vice President of Formulations and Principal Investigator of the contract awarded by the National Institutes of Health (NIH) that funded the trial. “An effective thermostable TB vaccine would not only be better suited to reach areas of the world most burdened by the disease, but it would also mitigate costs and reduce wastage associated with more stringent cold-chain storage requirements.”
TB spreads when infected people expel the bacterium into the air; TB claimed 1.6 million lives and infected 10.6 million people in 2021. The World Health Organization estimates that nearly 2 billion people across the globe are infected with Mtb. The COVID-19 pandemic impeded global progress toward control of TB by diverting resources from TB prevention and treatment efforts. Available resources were dedicated to combatting the COVID-19 pandemic, which also led to a reduction in TB case reporting, resulting in a later detection and treatment of TB and creating the opportunity for additional community transmission of infection. If proved effective in larger clinical trials, AAHI’s vaccine candidate will be a unique asset in the arsenal of control tools to reverse the resurgence of TB.
Additional studies will be needed to scaleup manufacturing and establish that the vaccine candidate will protect populations in low-resource communities most burdened by TB, such as in Southeast Asia and Sub-Saharan Africa, that struggle to maintain even simple refrigeration for vaccine transport and storage. By reducing the need for coldchain, AAHI’s TB vaccine candidate may significantly advance the global fight against TB.
“Equitable access to vaccines has been significantly impeded by cold-chain requirements and, as observed with COVID-19, no one is safe until everyone is safe,” explains Corey Casper, MD, MPH, Chief Executive Officer at AAHI. “The development of a safe and immunogenic temperature-stable TB vaccine is a major achievement towards our mission of bringing vaccines to people who most need them, regardless of geography.”
The research and development of the thermostable single-vial TB vaccine candidate received support from multiple partners: NIH/National Institute of Allergy and Infectious Diseases (NIAID), Saint Louis University, Lyophilization Technology Inc., Advanced Biosciences Laboratories, DF/Net Research, and the Center for Biocatalysis and Bioprocessing at the University of Iowa.
The project described here is supported by NIAID contract HHSN272201400041C. The views and conclusions contained herein are those of the authors and should not be interpreted as necessarily representing the official policies or endorsements, either expressed or implied, of the U.S. Government.