A whole-cell inactivated vaccine for improved protection against tuberculosis

PROJECT SUMMARY/ABSTRACT Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is the world's deadliest infectious disease. Approximately 10.6 million people fell ill from TB in 2022, resulting in 1.6 million deaths globally1. These alarming numbers demonstrate the critical need for effective TB prevention and treatment worldwide. The commercially available vaccine Bacille Calmette Guérin (BCG) effectively prevents systemic infection that occurs in children, but poorly protects against the more common pulmonary infection in adults. Additionally, BCG does not elicit mucosal immunity in the lungs, which is a major reason BCG vaccination does not protect adults adequately. We have developed SolaVAX-TB, a whole-cell inactivated Mtb vaccine, to address the significant unmet need for a scalable and cost-effective vaccine that triggers both systemic and pulmonary immunity. SolaVAX-TB is created using the photosensitizer riboflavin (Vitamin B2) and ultraviolet (UV) light to disrupt pathogen genetic material while preserving antigenic integrity. SolaVAX-TB shows in vivo efficacy as a BCG booster when administered both intramuscularly (IM; systemic immunity) or intranasally (IN; mucosal/lung immunity; Fig. 2). In new preliminary data, we now show significant long-term (up to 90 days) pulmonary protection by IN SolaVAX-TB delivered in combination with the potent mucosal adjuvant MucosImmune (nanoparticle liposomal-dual TLR complexes) following initial BCG prime vaccination (Fig. 3). Here, we will evaluate the safety, immunogenicity, and efficacy of mucosal SolaVAX-TB. Aim 1 will test our vaccine against alternative whole-cell vaccine candidates. Aim 2 will evaluate the long-term protective efficacy of IN SolaVAX-TB as a boost for conventional BCG vaccination and as a stand-alone vaccine against pulmonary challenge with high-virulence Mtb. Collectively, these studies will provide the basis for furthering development of SolaVAX-TB toward IND and ultimately, the clinic.