Synthetic Particulate Subunit Vaccines for the Prevention of Q Fever.

Abstract

Coxiella 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 1000 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.