Development of Surrogate Biomarkers for Supporting Clinical Trials of Human Leptospirosis Vaccines

About This Grant

Luna Bioscience, Inc., a Connecticut-based company spun out from Yale University, is dedicated to developing a vaccine to prevent human leptospirosis, a significant zoonotic bacterial disease. Leptospirosis affects over 1 million people annually with a high fatality rate of 5-20%. This project addresses the urgent need for a safe and effective human leptospirosis vaccine by creating reliable surrogate markers for vaccine-induced protection. The innovative aspect of this project is the development of simple in vitro tests to predict vaccine efficacy based on a new Virulence Modifying (VM) protein-based vaccine candidate, backed by preliminary data showing protection in animal models. There is currently no pan-effective human leptospirosis vaccine. Existing animal vaccines are unsuitable for humans due to efficacy and safety concerns. This project aims to close the gap by developing surrogate markers to predict vaccine efficacy, focusing on the VM protein family. We hypothesize that antibodies induced by VM protein vaccines will provide protective immunity, and in vitro tests based on antibody interruption of VM protein functions (DNase activity, target cell binding, cytotoxicity) will predict this immunity. The specific aims are to (1) develop in vitro assays measuring IgG antibody inhibition of VM protein functions, using purified IgG from vaccinated dogs and hamsters, and (2) benchmark these markers against lethal challenge with various Leptospira interrogans serovars in hamsters after both vaccination and passive transfer of immune vs. control sera. Success will yield surrogate markers of efficacy that can support human clinical trials and potentially yield a leptospirosis vaccine with important domestic and American military health implications, as well as creating new markers for Luna's leptospirosis products in low and middle-income countries (LMICs) and high- income countries with specific populations at risk. Key milestones include the identification of surrogate markers predicting protective immunity, and the development of in vitro tests correlating with protective immunity in the hamster model. This Phase I project will be the basis for future collaboration with contract development and manufacturing organizations (CDMOs) to develop a cGMP-compatible manufacturing process and an analytical assay portfolio. Luna Bioscience aims to first commercialize a VM protein-based leptospirosis vaccine for dogs, with assays to predict vaccine efficacy critical for FDA IND submission for human trials. By addressing these aims, the project will lay the foundation for a new effective vaccine against human leptospirosis, filling a significant unmet medical need.