Synthetic Particulate Subunit Vaccines for the Prevention of Q Fever.

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 we developed a safe particulate subunit vaccine candidate that is ambient-temperature stable and can be cost-effectively manufactured. We bioengineered endotoxin-free Escherichia coli 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 were ambient-temperature stable. Safety and immunogenicity were confirmed in mice and guinea pig models. YbgF-BP-Com1 elicited specific and strong humoral immune responses in guinea pigs with IgG titers that were at least 1000 times higher than those induced by Q-VAX ® . BP vaccine candidates were not reactogenic. After challenge with C. burnetii, YbgF-BP-Com1 vaccine led 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 suggested that YbgF-BP-Com1 induces functional immune responses reducing infection by C. burnetii. Collectively, our findings illustrate the potential of BPs as an effective antigen carrier for Q fever vaccine development. This article is protected by copyright. All rights reserved.