Breakthrough 'temperature-stable' tuberculosis vaccine in early trials

On Monday, researchers at the Access to Advanced Health Institute (AAHI) announced positive results from the phase 1 clinical trial of a tuberculosis (TB) vaccine that can be freeze-dried and stored at higher temperatures for several months without any harm, according to a press release.

The development is significant for fighting the world’s second deadliest infectious disease and overcoming a significant obstacle to vaccine distribution in less wealthy areas of the world.

The vaccine combines various proteins from the bacterium that causes TB

AAHI's TB vaccine is a freeze-dried formulation that combines various proteins from Mycobacterium tuberculosis into a fusion protein known as "ID93." Containing a unique immune-stimulating adjuvant called "GLA-SE," the vaccine can be safely stored at elevated temperatures, approximately 100 degrees Fahrenheit (37 °C), for several months.

The new freeze-dried TB vaccine candidate presented in a single vial was found to generate a more robust immune response than administration of the same vaccine using separate vials of antigen and liquid adjuvant formulation.

The trial assessed the safety, tolerability, and immunogenicity of the temperature-stable, freeze-dried, and single-vial vaccine candidate compared to the previous version of the vaccine, which was presented in two vials and had shown encouraging results in Phase 2 clinical trials.

The results of the trial have shown that the new vaccine is safe and well-tolerated, and it produced measurable cellular and antibody responses. The temperature-stable version of the vaccine also generated higher levels of antibodies in the blood compared to the previous non-stable version.

However, the researchers warned that the results are not enough to definitively prove which vaccine provides the most protection against TB.

"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," said Christopher Fox, Ph.D., 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."

The results of the study were published in Nature Communications.

Study abstract:

Adjuvant-containing subunit vaccines represent a promising approach for protection against tuberculosis (TB), but current candidates require refrigerated storage. Here we present results from a randomized, double-blinded Phase 1 clinical trial (NCT03722472) evaluating the safety, tolerability, and immunogenicity of a thermostable lyophilized single-vial presentation of the ID93 + GLA-SE vaccine candidate compared to the non-thermostable two-vial vaccine presentation in healthy adults. Participants were monitored for primary, secondary, and exploratory endpoints following intramuscular administration of two vaccine doses 56 days apart. Primary endpoints included local and systemic reactogenicity and adverse events. Secondary endpoints included antigen-specific antibody (IgG) and cellular immune responses (cytokine-producing peripheral blood mononuclear cells and T cells). Both vaccine presentations are safe and well tolerated and elicit robust antigen-specific serum antibody and Th1-type cellular immune responses. Compared to the non-thermostable presentation, the thermostable vaccine formulation generates greater serum antibody responses (p < 0.05) and more antibody-secreting cells (p < 0.05). In this work, we show the thermostable ID93 + GLA-SE vaccine candidate is safe and immunogenic in healthy adults.