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1944 年落矶山斑点热疫苗的基因测序。

Genetic sequencing of a 1944 Rocky Mountain spotted fever vaccine.

机构信息

Viral Pathogenesis and Evolution Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 33 North Drive MSC 3203, Bethesda, MD, 20892-3203, USA.

Coxiella Pathogenesis Section, Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.

出版信息

Sci Rep. 2023 Mar 22;13(1):4687. doi: 10.1038/s41598-023-31894-0.

Abstract

Rocky Mountain spotted fever (RMSF) is a rapidly progressive and often fatal tick-borne disease caused by Rickettsia rickettsii. Its discovery and characterization by Howard Ricketts has been hailed as a remarkable historical example of detection and control of an emerging infectious disease, and subsequently led to the establishment of the Rocky Mountain Laboratories (RML). Here, we examined an unopened bottle of a vaccine, labeled as containing RMSF inactivated by phenol-formalin of infected ticks, developed prior to 1944 at RML by DNA analysis using Illumina high throughput sequencing technology. We found that it contains DNA from the Rocky Mountain wood tick (Dermacentor andersoni), the vector of RMSF, the complete genome of Rickettsia rickettsii, the pathogen of RMSF, as well as the complete genome of Coxiella burnetii, the pathogen of Q-fever. In addition to genomic reads of Rickettsia rickettsii and Coxiella burnetii, smaller percentages of the reads are from Rickettsia rhipicephali and Arsenophonus nasoniae, suggesting that the infected ticks used to prepare the vaccine carried more than one pathogen. Together, these findings suggest that this early vaccine was likely a bivalent vaccine for RMSF and Q-fever. This study is the among the first molecular level examinations of an historically important vaccine.

摘要

落矶山斑点热(RMSF)是一种由立克次体引起的迅速进展且常致命的蜱传疾病。它由 Howard Ricketts 发现并鉴定,被誉为检测和控制新兴传染病的卓越历史范例,并随后促成了落矶山实验室(RML)的建立。在这里,我们通过使用 Illumina 高通量测序技术对 DNA 进行分析,检查了一瓶未开封的疫苗,该疫苗标签上注明含有通过感染蜱的苯酚甲醛灭活的 RMSF,该疫苗由 RML 于 1944 年之前开发。我们发现它包含了来自落矶山木蜱(Dermacentor andersoni)的 DNA,RMSF 的传播媒介,RMSF 病原体立克次体的完整基因组,以及 Q 热病原体贝氏柯克斯体的完整基因组。除了立克次体和贝氏柯克斯体的基因组读数外,还有较小比例的读数来自立氏立克次体和 Arsenophonus nasoniae,这表明用于制备疫苗的感染蜱携带了不止一种病原体。这些发现表明,这种早期疫苗可能是 RMSF 和 Q 热的双价疫苗。本研究是对历史上重要疫苗进行的首批分子水平检查之一。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/197c/10033921/61fe7c89c07d/41598_2023_31894_Fig1_HTML.jpg

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