1. Synthetic Particulate Subunit Vaccines for the Prevention of Q Fever.
- Author
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Sam G, Plain K, Chen S, Islam A, Westman ME, Marsh I, Stenos J, Graves SR, and Rehm BHA
- Subjects
- Humans, Animals, Mice, Guinea Pigs, Bacterial Vaccines, Immunity, Vaccines, Subunit metabolism, Q Fever prevention & control, Coxiella burnetii metabolism
- 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 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., (© 2024 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.)- Published
- 2024
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