Sttr phase i: recombinant BCG as a novel immunoadjuvant for viral infections

This Project Grant from the National Science Foundation's Technology, Innovation, and Partnerships program totaling $256,000 will develop Recombinant BCG as a novel immunoadjuvant for viral infections. The awardee, Oncosting LLC located in Baltimore, Maryland, will optimize media and lyophilization manufacturing of BCG-STING, evaluate its immunological effects as an adjuvant for H1N1 influenza vaccination, and assess its protective effects as an H1N1 vaccine adjuvant. By adding stimulator of interferon genes agonist overproduction to Bacillus Calmette-Guérin, the recombinant BCG serves dual purposes of enhancing trained immunity in macrophages conferred by BCG and promoting critical antiviral interferon responses. If successful, this proof-of-concept work could advance a next-generation vaccine adjuvant platform to strengthen vaccine efficacy against a wide range of infections, helping address diseases like seasonal influenza that significantly burden public health.

Abstract

The broader impact /commercial potential of this small business technology transfer (sttr) phase i project improves treatment of viral conditions, starting with influenza. Each year seasonal influenza infects 9?35 million individuals, causes 56,000 deaths in the U.S., and costs $87.1 billion. The proposed technology has the potential to produce more rapid protection, expand pathogen/variant coverage, and extend the longevity of protection afforded by influenza vaccination and other vaccines. This added protection will reduce the high healthcare costs and productivity losses due to mortality/morbidity. This technology has the potential to serve as a rapidly deployable prophylactic or vaccine adjuvant to enhance protection and reduce the necessary vaccine dose, expanding access and providing a timelier response. This small business technology transfer phase i project advances a next-generation vaccine adjuvant platform. While vaccines represent a major medical success, several diseases have proven difficult to address, including seasonal and pandemic influenza, tuberculosis (TB), malaria, hepatitis c virus (HCV), and HIV. One way to improve the efficacy of vaccines for these diseases is to use an adjuvant to strengthen the immune response to the antigen presented via vaccination. The proposed technology has the potential to enhance the efficacy of vaccines against a wide range of infections directly and via heterologous immunity because the addition of ?stimulator of interferon genes? (sting) agonist overproduction to bacillus calmette-GU?RIN (BCG) serves a dual purpose: IT enhances the elevated trained immunity of macrophages already known to be conferred by BCG and promotes critical antiviral IFN-i responses. The key objectives for this project are: 1) optimize media and lyophilization for manufacturing of BCG-sting; 2) evaluate the immunological effects of BCG-sting as an adjuvant for H1N1 influenza vaccination; and 3) assess the protective effects of BCG-sting as an adjuvant for H1N1 vaccination. This will provide proof of concept for proceeding with the development of this novel recombinant BCG as an efficacy-boosting adjuvant that also offers intrinsic antiviral immunity. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the foundation's intellectual merit and broader impacts review criteria.