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用重组F1-V疫苗接种的转染色体牛产生的多克隆抗体可增强体外细菌调理作用,并保护小鼠免受肺鼠疫感染。

Polyclonal Antibodies Derived from Transchromosomic Bovines Vaccinated with the Recombinant F1-V Vaccine Increase Bacterial Opsonization In Vitro and Protect Mice from Pneumonic Plague.

作者信息

Biryukov Sergei S, Wu Hua, Dankmeyer Jennifer L, Rill Nathaniel O, Klimko Christopher P, Egland Kristi A, Shoe Jennifer L, Hunter Melissa, Fetterer David P, Qiu Ju, Davies Michael L, Bausch Christoph L, Sullivan Eddie J, Luke Thomas, Cote Christopher K

机构信息

Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA.

SAB Biotherapeutics, 2100 E 54th St. N, Sioux Falls, SD 57104, USA.

出版信息

Antibodies (Basel). 2023 May 8;12(2):33. doi: 10.3390/antib12020033.

Abstract

Plague is an ancient disease that continues to be of concern to both the public health and biodefense research communities. Pneumonic plague is caused by hematogenous spread of bacteria from a ruptured bubo to the lungs or by directly inhaling aerosolized bacteria. The fatality rate associated with pneumonic plague is significant unless effective antibiotic therapy is initiated soon after an early and accurate diagnosis is made. As with all bacterial pathogens, drug resistance is a primary concern when developing strategies to combat these infections in the future. While there has been significant progress in vaccine development, no FDA-approved vaccine strategy exists; thus, other medical countermeasures are needed. Antibody treatment has been shown to be effective in animal models of plague. We produced fully human polyclonal antibodies in transchromosomic bovines vaccinated with the recombinant F1-V plague vaccine. The resulting human antibodies opsonized bacteria in the presence of RAW264.7 cells and afforded significant protection to BALB/c mice after exposure to aerosolized . These data demonstrate the utility of this technology to produce large quantities of non-immunogenic anti-plague human antibodies to prevent or possibly treat pneumonic plague in human.

摘要

鼠疫是一种古老的疾病,仍然受到公共卫生和生物防御研究界的关注。肺鼠疫是由细菌从破裂的腹股沟淋巴结通过血行播散至肺部或直接吸入雾化细菌引起的。除非在早期准确诊断后不久就开始有效的抗生素治疗,否则与肺鼠疫相关的死亡率很高。与所有细菌病原体一样,在制定未来对抗这些感染的策略时,耐药性是一个主要问题。虽然疫苗开发取得了重大进展,但尚无美国食品药品监督管理局(FDA)批准的疫苗策略;因此,需要其他医学应对措施。抗体治疗已被证明在鼠疫动物模型中有效。我们在用重组F1-V鼠疫疫苗接种的转染色体牛中产生了完全人源多克隆抗体。所得的人源抗体在RAW264.7细胞存在的情况下调理细菌,并在BALB/c小鼠暴露于雾化菌后提供了显著的保护。这些数据证明了该技术在生产大量非免疫原性抗鼠疫人源抗体以预防或可能治疗人类肺鼠疫方面的实用性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f033/10204441/cad9e0b4a733/antibodies-12-00033-g001.jpg

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