Diphtheria Toxoid Particles as Q Fever Vaccine

Abstract

AbstractThere is an unmet need for a stable and nonreactogenic vaccine against the bioterrorism agent, Coxiella burnetii, causing Q fever. Here a safe, effective, and non‐reactogenic Q fever vaccine is developed by employing self‐assembled particles (CPs) composed of cross‐reacting material 197, a nontoxic variant of diphtheria toxin. CPs are designed that incorporate selected C. burnetii antigens and assemble them inside engineered Escherichia coli at high yields. A cost‐effective manufacturing process enables the production of CP‐based Q fever vaccine candidates. Four vaccine candidates are developed, including a T‐cell epitope‐based vaccine (CP‐COX), and one that comprises two immunodominant antigens, Com1 and YbgF. The latter is tested separately (CP‐Com1, CP‐YbgF) or as a mixture (CP‐Com1/CP‐YbgF). Initial immunogenicity studies in mice reveal that the mixed CP‐Com1/YbgF elicits the highest antibody titers with a half maximal effective concentration (EC50) value of ≈100 000 and induction of TH1 and TH2 cytokines. CP‐Com1/YbgF is further evaluated in guinea pigs, demonstrating its safety and efficacy, as shown by the absence of adverse reactions and a significant reduction in febrile responses compared to alum upon challenge with C. burnetii. Together, the study shows the potential of CPs for the development of a safe and immunogenic subunit Q fever vaccine.