Major Research Project RP009
Collaborating Institution: Texas A&M University System Health Science Center (TAMUSHSC), College Station, TX
Principal Investigator: James Samuel, PhD
Title of the Project: Development of a Subunit Vaccine Against Q Fever
Co-Investigator: Laura Hendrix, PhD – TAMUSHSC, College Station, TX
Collaborator: Roy Curtiss III, PhD – Arizona State University, Tempe, AZ
Expected Product: Development of a Q fever vaccine.
Description: A vaccine against Q fever remains an important public health and national security goal. While whole cell vaccines have proven efficacious, they have also caused significant adverse localized and systemic reactions, limiting the potential for approval as human vaccine in US. The long-term goal of this application is to understand the mechanisms of vaccine-induced and infection-derived protection against C. burnetii infection leading to the development of an efficacious vaccine. The central hypothesis is that both cellular and humoral immunity play essential roles in long-lived immunity against C. burnetii infection. Both LPS and immunogenic proteins have been identified as key components to the humoral and cell-mediated immune responses.
Our design strategy is to develop soluble protein based vaccines that confer protective immunity by either pooling immunogenic proteins or conjugating immune-reactive recombinant proteins to LPS. The vaccine candidates will be characterized for the protective capacity in BL6 and MHC II-humanized (DR1 or DR4) mice and outbred guinea pigs. We will accomplish the objective by pursuing the following specific aims:
- Heterologously express O polysaccharide as an N-linked glycoprotein. Protective carbohydrate epitopes on the O-side chain of C. burnetii LPS will be expressed as an N-linked glycoprotein using the transferase (PglB) and acceptor (AcrA) proteins from Campylobacter jejuni. The coupled O side chain carbohydrates will be purified, and structurally and antigenically characterized. A C. burnetii antigenic protein (Com-1) will be modified with an acceptor motif to replace AcrA and evaluated for the ability to act as an antigenic N-linked carrier protein.
- Evaluate the protective capacity of recombinant proteins and LPS-conjugated proteins to confer protection in the intratracheal mouse model. At least 35 recombinant proteins will be characterized in the protection assays, chosen based on their ability to serve as strong T cell antigens.
- Test the ability of solubilized proteins from C. burnetii, RSA439 (Select Agent exempt, requiring only BSL2 containment) that do not elicit significant hypersensitivity in guinea pig skin test model to confer protection in mice. Based on recent progress with in vitro cultivation, production of this avirulent C. burnetii strain provides the commercial potential to produce a soluble and safe vaccine alternative to subunit vaccine design.