B.abortus-based vaccine against viral hemorrhagic fevers

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DESCRIPTION (provided by applicant): Viral hemorrhagic fevers (VHF) are severe and life-threatening diseases caused by several viruses. Lassa virus, Crimean/Congo hemorrhagic fever virus, Marburg and Ebola viruses are four of the VHF causing agents known to be readily capable of person-to-person spread. No vaccines against these viral diseases are currently available. With the recent heightened bioterror threat, the potential use of these deadly viruses by terrorist elements has become apparent. Moreover, availability of safe and effective vaccines against VHF agents will be useful for protecting people with high risk of getting exposed to these viruses, such as people traveling to or living in the endemic regions of Africa. Research conducted to date demonstrates that both antibody and cell-mediated immune responses are necessary for protection to VHFs. The overall objective of the proposed research project is to develop a highly efficacious and safe vaccine for VHF. Specifically, the investigators propose to prepare an effective vaccine against VHF by expressing previously identified protective protein(s) of Ebola and Lassa viruses in Brucella abortus strain RB51, a bacterial vector with unique adjuvant properties and can stimulate a strong cell-mediated immune response. In the current proposal, the investigators intend to i) construct recombinant RB51 strains that express nucleoprotein and partial glycoprotein of Lassa and Ebola viruses, and ii) immunize mice with irradiated recombinant RB51 vaccines and characterize their antigen-specific antibody and cell-mediated immune responses. Recent research conducted by the investigators indicate that recombinant RB51 strains exposed to low doses of gamma radiation are unable to replicate but induce strong immune responses after just one immunization. Therefore, the investigators propose to use irradiated recombinant RB51 strains to immunize mice parentally and mucosally and study the specific immune responses. The proposed studies will clearly demonstrate the proof-of-concept for the development of efficacious and safe vaccines against viral diseases using irradiated, recombinant RB51 strain as a novel expression and delivery platform.