SBIR-STTR Award

The goal of this proposal is to further the development of a vaccine designed to offer protection from Clostridium difficile disease. The results of previous vaccination experiments incorporating mucosal immunization demonstrate the feasibility of a vaccine for this disease. Clinical development will require a scaleable manufacturing process to produce the amount of antigen needed for mucosal administration. Antigen production methods which improve yield and purity will be determined and refined. Immunization studies using the improved formulations will define the vaccination regimen which confers optimal protection to animals and conforms to requirements for clinical administration. Nosocomial infection of the elderly with C. difficile often results in significant morbidity and increased length of hospital stays. The health care costs due to prolonged hospitalization, diagnostic testing and specific C. difficile therapy are substantial. Antibiotic therapy for C. difficile infection is reasonably effective but the relapse rate is high. Vaccination of patients at risk will stimulate host immunity to this disease thereby offering a more cost-effective preventative strategy to control C. difficile infection. The results of these experiments will provide a basis for Phase II studies in which we will identify a final manufacturing process and perform a clinical safety trial.Proposed commercial application:Clostridium difficile infection is one of the leading nosocomial diseases in the U.S. As the primary etiological agent of antibiotic-associated diarrhea, this organism is responsible for considerable discomfort and increased health care costs. C. difficile disease is vaccine preventable. Immunization provides a cost-effective strategy that would result in substantial savings in medical costs and reduced morbidity.National Institute of Allergy and Infectious Diseases (NIAID)

The goal of the proposed research is to develop a vaccine and/or antibody preparation useful for prevention and treatment of Clostridium difficile associated diarrhea (CDAD). Parenteral vaccination with C. difficile toxoid in animal models of a)AD has demonstrated protection from challenge. Furthermore, parenterally administered toxin neutralizing antibodies can protect animals from CDAD. Antigen production methods have been developed and will be used to manufacture vaccine for clinical testing. Plasma donors will be immunized with the vaccine to produce hyperimmune globulin preparations for use in treating and preventing CDAD in clinical trials. Nosocomial infection of the elderly with C. difficile often results in significant morbidity and increased length of hospital stays in spite of effective therapies. The health care costs due to prolonged hospitalization, diagnostic testing and specific C. difficile therapy are substantial. Immunotherapy of patients infected with C. difficile or at risk would offer a cost-effective preventative strategy to control C. difficile infection. Passive immunization can rapidly protect individuals at risk and will pave the way for active vaccine development by defining protective levels of antitoxin antibodies in humans. The goal of rapid and long term protection could be achieved using immune globulin strategies along with the vaccine. PROPOSED COMMERCIAL APPLICATION: Clostridium difficile infection is one of the leading nosocomial diseases in the U.S. As the primary etiological agent of antibiotic-associated diarrhea, this organism is responsible for considerable discomfort and increased health care costs. C. difficile disease is vaccine preventable. Immunotherapy provides a cost-effective strategy that would result in substantial savings in medical costs and reduced morbidity