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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.

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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