A Serological Assay for Neutralizing Antitoxin Response in Patients with Clostridioides difficile Infection (Phase II)

Abstract This SBIR Phase II project will support the development of an in vitro diagnostic blood test to determine whether a person infected with Clostridioides difficile has mounted enough neutralizing antitoxin antibodies so that they are unlikely to suffer recurrence. Antibiotic-resistant C. difficile is responsible for more than 29,000 deaths in the US each year and the infection is an urgent threat to public health worldwide. The current standard treatment with antibiotics disrupts gut microbiota and induces high rates of recurrence, which is the most significant issue in clinical management of the disease. C. difficile infection (CDI) is mainly caused by two major exotoxins, and toxin-neutralizing antibodies are responsible for effective immunity. However, current assays to measure patient antitoxin responses are based on cell-culture neutralizing bioassay that is time consuming, laborious, and difficult to standardize, thus such bioassay is limited in research laboratories. In our SBIR Phase I (R43AI136176) study, we successfully established a simple and rapid serological ELISA, designated as BB-ELISA, and demonstrated that the BB-ELISA was able to measure antitoxin neutralizing activities in CDI blood samples. Based on these promising results, we propose to standardize this novel BB- ELISA through an experience CRO Corgenix and to collaborate with Merck to evaluate the assay for predicting CDI disease recurrence and outcomes. The completion of this Phase II SBIR will not only validate this novel ELISA for measuring neutralizing antibody responses in CDI patients and predicting disease outcomes, but also pave the way toward future commercialization of this novel ELISA assay.