Q fever is an understudied infectious disease caused by Coxiella burnetti. Q-Vax, a formalin-inactivatedwhole bacteria, is currently the only human vaccine approved for Q fever. Attempts have been made todetermine the protective epitopes, but such studies have not advanced into an efficacious subunit vaccine.In addition, pre-exposure to C. burnetti, results in adverse reactions to Q-Vax. Given these collectiveconcerns, there is a need to develop an efficacious, preferably subunit vaccine that minimizes suchreactivities. The sequencing of C. burnetti genome enables selection of potential vaccine candidates,especially those proteins that are responsible for C. burnetti survival in the host phagolysosome as havesimilar proteins been identified in other bacteria and subsequently shown to confer protection. Thus, wehave identified 68 potential vaccine candidates that will be cloned into eukaryotic expression vectors for DNAvaccination. Using a reductionist approach (Specific Aim 1), candidates will be selected for their ability toreduce infection subsequent to live challenge using the phase I of Nine Mile C. burnetti strain (provided byCore A). In addition, information derived from Projects 1, 2, and 3 will also be used to assist in the selectionprocess. Once candidates are identified, these will be administered to mice and to guinea pigs in suitablecombinations with molecular adjuvants to enhance cell-mediated and/or humoral immunity (Specific Aim 2).We hypothesize that we can derive <8 candidates that will be eventually tested in a pneumonic challengestudy to determine efficacy of the derived vaccine(s) and a vaccination regimen (Specific Aim 3).Project interactions: This project will be closely integrated with other projects and with Core Facilitiesdescribed in this proposal. We will work closely with the other investigators in this program project: projects1,2, and 3.
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