作者: Marsh, Ian ; Plain, Karren ; Stenos, John ; Rehm, Bernd H. A. ; Islam, Aminul ; Graves, Stephen R. ; Chen, Shuxiong ; Sam, Gayathri ; Westman, Mark E.

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.

2023-12-28·The Journal of Physical Chemistry A

Computational Risk Assessment of Persistence, Bioaccumulation, and Toxicity of Novel Flame-Retardant Chemicals

Article

作者: Pandit, Shraddha ; Singh, Prakrity ; Sinha, Meetali ; Yadav, Dhvani ; Parthasarathi, Ramakrishnan

Novel brominated flame retardants (NBFRs) have emerged as chemicals of environmental concern, as they have been widely used as an alternative to polybrominated diphenyl ethers (PBDEs). Considering the similar structural features of NBFRs and PBDEs necessitates a comprehensive investigation to understand the physicochemical relationships of these compounds and their ability to alter biological functions. In this study, we investigated the persistent nature of NBFRs in terms of thyroid-disrupting potential by understanding the structure-stability aspects using density functional theory (DFT)-based reactivity parameters and interactions via molecular docking and molecular dynamics (MD) simulations. The results indicate that the DFT-based stability descriptor (chemical hardness) is associated with the persistent nature of NBFRs. The computed molecular interaction profile revealed prominent interactions between thyroid receptor-β (TR-β) and NBFRs. Stable trajectory and interactions with TR-β were obtained with ATE, p-TBX, PBT, PBEB, and TBBPA-DBPE during 100 ns of MD simulation. The results of these studies have suggested that the presence of a higher number of halogenated atoms increases the stability vis-à-vis the persistence and endocrine disruption potential of NBFRs.

2023-11-01·Future Microbiology

Q Fever – Immune Responses and Novel Vaccine Strategies

Review

作者: Stenos, John ; Norton, Robert ; Graves, Stephen ; Redden, Patricia ; Agnew, Linda ; Govan, Brenda ; Fourie, Phillip ; Ketheesan, Natkunam ; Parker, Kaitland ; Henderson, Sinead

Q fever is a zoonotic disease caused by the bacterium Coxiella burnetii. It is an occupational risk for employees of animal industries and is associated with contact with wildlife and domestic animals. Although Q fever infection may be asymptomatic, chronic sequelae such as endocarditis occur in 5% of symptomatic individuals. Disease outcomes may be predicted through measurement of immune correlates. Vaccination is the most efficient method to prevent Q fever. Currently, Q-VAX is the only licenced human vaccine. Q-VAX is highly effective; however, individuals previously exposed to C. burnetii are at risk of adverse reactions. This review examines the immunological responses of acute and chronic Q fever and the efforts to provide a safer and cost-effective Q fever vaccine.

100 项与 P-Vax 相关的药物交易

登录后查看更多信息