Assessing Immunogenicity of Vaccines and Adjuvant Combinations for Q Fever

Abstract

Abstract There is an unmet need for developing a safer, effective, single-dose vaccine for Coxiella burnetii conferring prolonged resistance, due to its high infectivity and biothreat potential. C. burnetii causes Q fever, which acutely causes fever-like symptoms but may manifest chronically and escalate into pneumonia and endocarditis. Prior sensitization has been documented to exacerbate the current vaccine’s reactogenicity and there have been considerable efforts in developing alternatives. Our lab has been studying the effects of combinations of adjuvants and their synergistic effects in eliciting antibody and T cell responses. Here we describe an effective adjuvant combination using synthetic TLR4 agonist monophosphoryl lipid A (MPLA), TLR9 agonist CpG ODN 1018, and Addavax, a squalene oil-in-water emulsion. In vitro assays were performed to assess the immunogenicity of these adjuvants in the context of NFκB activation and inducible nitric oxide synthase (iNOS) production. Model antigens from C. burnetii were selected based on previous protein microarray data and formulated with varying adjuvant combinations. These formulations were administered to C57BL/6 mice and assessed for immunogenicity. Sera collected at regular intervals were screened against protein microarrays to monitor the dynamics and isotypes of the antibody response. Here we observed robust, durable and antigen-specific T cell and antibody responses. Our top vaccine formulations were administered to Hartley guinea pigs in a challenge study. Initial data demonstrate specific IgG production against immunizing antigens. Downstream analysis for this data set is currently underway. Supported by DTRA contract HDTRA1-16-C-0009 DTRA grants HDTRA1-18-1-0035 and HDTRA1-18-1-0036