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 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