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Ability of Antibody against Coxiella burnetii LPS to confer Protective Immunity
Institution: Texas A&M University System Health Science Center (TAMUSHSC), College Station, TX
Principal Investigator: James Samuel, PhD
Co-Investigators: a)
Igor Almeida, DSc – University of Texas at El Paso, El
Paso, TX Expected Product:Subunit vaccine for Q fever, possibly as a conjugate vaccine between immunogenic, partially protective proteins and LPS or LPS-protective carbohydrate epitopes.
Description: The objective of this application is to characterize the role of antibody (Ab)-mediated immunity (AMI) against Coxiella burnetii infection. It is based on our observations that: (1) formalin-inactivated phase I vaccine (PI-V) generated complete protection against virulent C. burnetii challenge in BALB/c mice, but phase II vaccine (PII-V) did not confer significant protection; (2) PI-V and PII-V elicited different Ab responses, while cytokine responses were similar; (3) phase I lipopolysaccharide (PI-LPS) was able to induce a level of protection similar to PI-V while phase II lipopolysaccharide (PII-LPS) conferred no significant protection; and (4) passive transfer of immune serum (IS) from PI-V vaccinated mice induced a level of protection similar to PI-V vaccination in naive mice. The first specific aim is to characterize the role of AMI against C. burnetii infection. The working hypothesis is that Abs play a critical role in PI-V-induced protection against C. burnetii infection. We will evaluate the contribution of IS-induced protection against C. burnetii infection in intraperitoneal and aerosol challenged BALB/c mice and aerosol challenged guinea pigs. We will determine whether Abs are the active components of IS-induced protection and define the kinetics of passively transferred antibody protection. The second specific aim will determine the key protective antibody isotypes and epitope targets. The working hypothesis is that the target of AMI is LPS core and/or O-side chain polysaccharide. We will purify immunoglobulin from serum and establish whether the protective component of IS is antibody. We will then determine the isotype of protective AMI to develop a hypothesis on the mechanism of AMI. The epitopes recognized by AMI will be defined using highly purified LPS, and LPS components through immunizations and absorption experiments. As a complimentary approach, a panel of anti-C.burnetii LPS monoclonal antibodies (Mabs) will be generated and tested for the ability to confer immunity by passive transfer. These studies will provide the feasibility, proof-of-concept research to design a subunit vaccine, which we plan to submit as a product development proposal for the competing continuation application for the WRCE.
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