Analysis of A Baumannii Capsule as a Vaccine Candidate

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DESCRIPTION (provided by applicant): Acientobacter baumannii is a gram-negative bacillus, which was initially known for causing health-care associated infections. Most recently the experience in Iraq/Kuwait/Afghanistan has reaffirmed the importance of A. baumannii in causing infections in wounded combatants. Further the prevalence of multi-drug and pan- resistant isolates of A. baumannii is increasing, placing us at risk for entering a post-antibiotic era. As a result, the incidence of Acinetobacter infection in all venues is increasing worldwide. The changing epidemiology and incidence of infections due to Acinetobacter establishes it as a pathogen of increasing medical importance. Needless to say, treatment of infections due to Acinetobacter has become challenging. Improved outcomes will require the development of new preventative and/or therapeutic strategies. Unfortunately, significant knowledge gaps exist that need to be filled to accomplish these goals. Vaccine candidates need to by identified and assessed. Virtually nothing is known about capsular polysaccharides in A. baumannii. Surface polysaccharides such as capsule have formed the basis for several successful vaccines directed against extracellular pathogens such as H. influenzae type b, S. pneumoniae, and certain serotypes of N. meningitidis. This approach may also be practical for Acinetobacter. Therefore, the first goal of this proposal, to determine the number and relative prevalence of A. baumannii capsule serotypes, will be accomplished in aim 1. These data will lay the foundation for immunization and protection studies designed to assess capsule as a vaccine candidate, which will be completed in aim 2. Also in aim 2 studies will be performed to determine the structures of 3-5 of the most prevalent capsular serotypes. This information will be used to optimize the method and design of capsule- protein conjugates as needed to optimize immunogenicity. These data will also be used to predict possible immune reactivity to human epitopes. Lastly, structural data will be an additional means to assess the conservation of capsular epitopes. This proposal will generate new and important data and fill knowledge gaps necessary for the development of new preventive approaches to combat A. baumannii, a pathogen of increasing medical importance in the civilian, veteran, and active military populations.