Synthetic Particulate Subunit Vaccines for the Prevention of Q Fever

Abstract

AbstractCoxiella burnetti is an intracellular bacterium that causes Q fever, a disease of worldwide importance. Q‐VAX®, the approved human Q fever vaccine, is a whole cell vaccine associated with safety concerns. Here a safe particulate subunit vaccine candidate is developed that is ambient‐temperature stable and can be cost‐effectively manufactured. Endotoxin‐free Escherichia coli is bioengineered to efficiently self‐assemble biopolymer particles (BPs) that are densely coated with either strings of 18 T‐cell epitopes (COX‐BP) or two full‐length immunodominant antigens (YbgF‐BP‐Com1) all derived from C. burnetii. BP vaccine candidates are ambient‐temperature stable. Safety and immunogenicity are confirmed in mice and guinea pig (GP) models. YbgF‐BP‐Com1 elicits specific and strong humoral immune responses in GPs with IgG titers that are at least 1 000 times higher than those induced by Q‐VAX®. BP vaccine candidates are not reactogenic. After challenge with C. burnetii, YbgF‐BP‐Com1 vaccine leads to reduced fever responses and pathogen burden in the liver and the induction of proinflammatory cytokines IL‐12 and IFN‐γ inducible protein (IP‐10) when compared to negative control groups. These data suggest that YbgF‐BP‐Com1 induces functional immune responses reducing infection by C. burnetii. Collectively, these findings illustrate the potential of BPs as effective antigen carrier for Q fever vaccine development.