Tuberculosis (TB) is the leading cause of death from a single infectious agent, a bacterium called Mycobacterium tuberculosis. It is estimated that 25% of the world’s population is infected with M. tuberculosis, but only one TB vaccine is available (BCG), and its effectiveness is inconsistent. Despite recent decreases in the mortality of TB, TB disease still causes enormous human suffering. It is one of the major drivers of global inequity, highlighting the specific need for new and effective vaccines to prevent M. tuberculosis infection.
Tuberculosis Vaccines
Subunit vaccines for TB are especially desired as they use antigens that target all stages of M. tuberculosis infection and disease. Subunit vaccines are also safe for use in immunocompromised populations, such as persons living with HIV. However, effective subunit vaccines rely on adjuvants to stimulate the immune system. As TB is one of the leading causes of death worldwide for persons living with HIV, effective adjuvants for subunit vaccines are critical.
Novel Adjuvant EmT4™
To address this need for safe TB vaccines and adjuvants, Dr. Rhea Coler, Senior Investigator at the Center for Global Infectious Disease Research at Seattle Children’s Hospital, and her team evaluated the potential of synthetically produced Monophosphoryl lipid A (SyMLP), a TLR4-agonist, formulated in an oil-in-water- emulsion (EmT4™) as an effective adjuvant for driving vaccine-mediated immune responses to M. tuberculosis. The study demonstrated that EmT4™ was a potent adjuvant that enhanced immune responses and provided significant protection against M. tuberculosis in preclinical models.
“When EmT4™ was paired with TB vaccine candidates ID93 or ID91, EmT4™ stimulated strong activation of immune cells, drove TH1-biased immunity, and reduced bacterial burden following aerosol challenge with M. tuberculosis, in both standard and immunocompromised animal models. Furthermore, protection was observed across different TB strains in both young and aged preclinical models, highlighting EmT4™’s versatility and potential for broad use in global vaccination strategies,” shared Dr. Coler.
Dr. Coler and her team plan to complete additional safety and immunogenicity studies in larger animal models to advance EmT4™ toward clinical development. They also plan to test EmT4™’s compatibility with other TB vaccine antigens and EmT4™’s possible use post-infection vaccination or as a BCG booster.
Global Impact
New adjuvants for vaccines against M. tuberculosis have the potential to improve vaccine efficacy, increase vaccine coverage, enhance safety, and provide broader immunity than is currently available. Dr. Sean Gray, co-author and Vice President of Research & Development at PAI Life Sciences shared, “EmT4™ represents a novel approach to vaccine adjuvants as a synthetic more a scalable alternative to current formulations. EmT4™ potential as a low-cost candidate for inducing TH1-driven immunity against M. tuberculosis suggests that it could be a powerful tool to diversify and strengthen to the global TB vaccine pipeline.”
“We live in a time in which support for key public health programs is under scrutiny but being involved in the development of global vaccination strategies and next-generation vaccine candidates against TB gives me hope,” said Dr. Coler.
This paper is available in ImmunoHorizons, a fully open access peer-reviewed journal published by The American Association of Immunologists, committed to advancing the knowledge of immunology and immunology education.
