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使用基因改造的减毒活疫苗对蜱传恰菲埃立克体感染产生的持久免疫反应。

Prolonged immune response to tick-borne Ehrlichia chaffeensis infection using a genetically modified live vaccine.

作者信息

Madesh Swetha, McGill Jodi, Jaworski Deborah C, Ferm Jonathan, Ferm Dominica, Liu Huitao, Fitzwater Shawna, Nair Arathy, Hove Paidashe, Alizadeh Kimia, Knox Cheyenne, Thackrah Ashley, Ganta Roman R

机构信息

Center of Excellence for Vector-Borne Diseases, Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, United States of America; Department of Veterinary Pathobiology, College of Veterinary Medicine, Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, United States of America.

Department of Veterinary Microbiology & Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, IO 50011, United States of America.

出版信息

Vaccine. 2025 Feb 27;48:126730. doi: 10.1016/j.vaccine.2025.126730. Epub 2025 Jan 17.

DOI:10.1016/j.vaccine.2025.126730
PMID:39826432
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11839323/
Abstract

Ehrlichia chaffeensis, a tick transmitted rickettsial bacterium, causes monocytic ehrlichiosis in humans and dogs. Earlier, we demonstrated that dogs immunized with a mutant strain of E. chaffeensis having a functional disruption in the gene encoding the phage head-to-tail connector protein serves as a modified live vaccine (MLAV) capable of inducing immunity against intravenous and tick-transmitted infection challenges within one month of vaccination. In this follow-up investigation, we assessed the duration of MLAV-induced immunity for one-year period against tick-transmission infection challenge. Dogs vaccinated with the MLAV were subsequently exposed to wild-type E. chaffeensis via tick transmission at 4-, 8-, and 12-months post-vaccination. Unvaccinated controls showed higher infection rates during the one-month assessment following infection. In contrast, MLAV-immunized dogs rapidly cleared infections and exhibited significantly fewer systemic bacterial infections compared to unvaccinated controls. Robust E. chaffeensis-specific IgG and CD4 T-cell responses persisted throughout the assessment period. Our findings underscore the efficacy of MLAV in providing natural hosts with protection against E. chaffeensis infection for up to one year following infected tick exposure.

摘要

查菲埃立克体是一种由蜱传播的立克次氏体细菌,可引起人类和犬类的单核细胞埃立克体病。此前,我们证明,用编码噬菌体头尾连接蛋白的基因发生功能破坏的查菲埃立克体突变株免疫的犬,可作为一种改良活疫苗(MLAV),能够在接种疫苗后一个月内诱导针对静脉内和蜱传播感染攻击的免疫力。在这项后续研究中,我们评估了MLAV诱导的针对蜱传播感染攻击的免疫力持续一年的时间。用MLAV接种疫苗的犬随后在接种疫苗后4个月、8个月和12个月通过蜱传播接触野生型查菲埃立克体。未接种疫苗的对照犬在感染后的一个月评估期间显示出较高的感染率。相比之下,与未接种疫苗的对照犬相比,MLAV免疫的犬迅速清除感染,全身细菌感染显著减少。在整个评估期间,强大的查菲埃立克体特异性IgG和CD4 T细胞反应持续存在。我们的研究结果强调了MLAV在为天然宿主提供保护,使其在接触感染蜱后长达一年的时间内免受查菲埃立克体感染方面的有效性。

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本文引用的文献

1
Long-Term Protective Immunity against Infection Induced by a Genetically Modified Live Vaccine.基因工程减毒活疫苗诱导的针对感染的长期保护性免疫
Vaccines (Basel). 2024 Aug 9;12(8):903. doi: 10.3390/vaccines12080903.
2
Genetically modified live vaccine offers protective immunity against wild-type Anaplasma marginale tick-transmission challenge.基因工程活疫苗对野生型边缘无浆体经蜱传播的挑战提供了保护免疫。
Vaccine. 2024 Oct 24;42(24):126069. doi: 10.1016/j.vaccine.2024.06.036. Epub 2024 Jun 15.
3
Efficacy and Immune Correlates of OMP-1B and VirB2-4 Vaccines for Protection of Dogs from Tick Transmission of Ehrlichia chaffeensis.
OMP-1B 和 VirB2-4 疫苗对犬预防埃立克体属蜱传感染的功效和免疫相关性。
mBio. 2022 Dec 20;13(6):e0214022. doi: 10.1128/mbio.02140-22. Epub 2022 Nov 7.
4
Targeted mutagenesis in Anaplasma marginale to define virulence and vaccine development against bovine anaplasmosis.在边缘无浆体中进行靶向突变以定义牛无浆体病的毒力和疫苗开发。
PLoS Pathog. 2022 May 16;18(5):e1010540. doi: 10.1371/journal.ppat.1010540. eCollection 2022 May.
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Mutations in Ehrlichia chaffeensis Genes ECH_0660 and ECH_0665 Cause Transcriptional Changes in Response to Zinc or Iron Limitation.恙虫病东方体基因 ECH_0660 和 ECH_0665 的突变导致对锌或铁限制的转录变化。
J Bacteriol. 2021 Jun 8;203(13):e0002721. doi: 10.1128/JB.00027-21.
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Multiple Ehrlichia chaffeensis Genes Critical for Its Persistent Infection in a Vertebrate Host Are Identified by Random Mutagenesis Coupled with Infection Assessment.通过随机诱变结合感染评估鉴定出对嗜吞噬细胞无形体在脊椎动物宿主中持续感染至关重要的多个基因。
Infect Immun. 2020 Sep 18;88(10). doi: 10.1128/IAI.00316-20.
7
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Immunity. 2019 Dec 17;51(6):1088-1101.e5. doi: 10.1016/j.immuni.2019.10.004. Epub 2019 Nov 12.
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