Efficacy and Immune Correlates of OMP-1B and VirB2-4 Vaccines for Protection of Dogs from Tick Transmission of Ehrlichia chaffeensis.
Efficacy and Immune Correlates of OMP-1B and VirB2-4 Vaccines for Protection of Dogs from Tick Transmission of Ehrlichia chaffeensis.
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DOI：
10.1128/mbio.02140-22
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发表时间：
2022-12-20
期刊：
影响因子：
6.4
通讯作者：
Rikihisa, Yasuko
中科院分区：
文献类型：
--
作者：
Budachetri, Khemraj;Lin, Mingqun;Chien, Rory C.;Zhang, Wenqing;Brock, Guy Nathaniel;Rikihisa, Yasuko
沙菲埃立体是一种必需的细胞内细菌，可引起人类单核细胞埃立体病，这是一种由孤星蜱传播的新疾病，美洲弱视虫。在这里，我们研究了OMP-1B和VirB2-4的疫苗潜力。在高表达且免疫优势的沙非伊蚊孔蛋白P28s/OMP-1s中，OMP-1B主要由沙非伊蚊在美洲蜱中表达，而VirB2-4是沙非伊蚊感染宿主细胞所必需的IV型分泌系统的菌毛蛋白。重组OMP-1B （rOMP-1B）或重组VirB2-4 （rVirB2-4）免疫小鼠对沙菲埃氏体感染的保护作用与埃利希体免疫的入口触发蛋白一样有效。狗接种了由rOMP-1B或rVirB2-4和免疫刺激复合物组成的纳米颗粒疫苗后，对各自的抗原产生了高抗体滴度。在蜱虫附着后的第3天或第6天以及实验期间，被感染沙菲纳伊虫的美洲蜱虫攻击的rOMP-1B或rVirB2-4免疫犬的血液中检测不到沙菲纳伊虫，而单独接种该复合物的狗在实验期间持续感染沙菲纳伊虫。沙非伊虫在吸血蜱中呈指数复制，以促进传播。从免疫过omp - 1b的狗身上移除的先前感染的蜱虫，其细菌载量明显低于从假免疫的狗身上移除的蜱虫，这表明蜱虫内中和作用。elisa检测和逆转录定量PCR结果显示，接种rvirb2 -4疫苗的狗外周血白细胞在蜱虫附着后分泌的干扰素-γ量显著升高，提示干扰素-γ介导的埃利希体抑制作用。因此，埃利希体表面暴露蛋白OMP-1B和VirB2-4代表了阻断蜱传埃利希体传播的新的潜在候选疫苗。
Ehrlichia chaffeensis, an obligatory intracellular bacterium, causes human monocytic ehrlichiosis, an emerging disease transmitted by the Lone Star tick, Amblyomma americanum. Here, we investigated the vaccine potential of OMP-1B and VirB2-4. Among the highly expressed and immunodominant E. chaffeensis porin P28s/OMP-1s, OMP-1B is predominantly expressed by E. chaffeensis in A. americanum ticks, whereas VirB2-4 is a pilus protein of the type IV secretion system essential for E. chaffeensis infection of host cells. Immunization with recombinant OMP-1B (rOMP-1B) or recombinant VirB2-4 (rVirB2-4) protected mice from E. chaffeensis infection as effectively as Entry-triggering protein of Ehrlichia immunization. Dogs vaccinated with a nanoparticle vaccine composed of rOMP-1B or rVirB2-4 and an immunostimulating complex developed high antibody titers against the respective antigen. Upon challenge with E. chaffeensis-infected A. americanum ticks, E. chaffeensis was undetectable in the blood of rOMP-1B or rVirB2-4 immunized dogs on day 3 or 6 post-tick attachment and for the duration of the experiment, whereas dogs sham-vaccinated with the complex alone were persistently infected for the duration of the experiment. E. chaffeensis exponentially replicates in blood-feeding ticks to facilitate transmission. Previously infected ticks removed from OMP-1B-immunized dogs showed significantly lower bacterial load relative to ticks removed from sham-immunized dogs, suggesting in-tick neutralization. Peripheral blood leukocytes from rVirB2-4-vaccinated dogs secreted significantly elevated amounts of interferon-γ soon after tick attachment by ELISpot assay and reverse transcription-quantitative PCR, suggesting interferon-γ-mediated Ehrlichia inhibition. Thus, Ehrlichia surface-exposed proteins OMP-1B and VirB2-4 represent new potential vaccine candidates for blocking tick-borne ehrlichial transmission.
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影响因子：
3.3
作者：
Kotál J;Langhansová H;Lieskovská J;Andersen JF;Francischetti IM;Chavakis T;Kopecký J;Pedra JH;Kotsyfakis M;Chmelař J
通讯作者：
Chmelař J
DOI：
10.1111/jsap.12431
发表时间：
2016-01-01
期刊：
The Journal of small animal practice
影响因子：
--
作者：
Day, M J;Horzinek, M C;Squires, R A
通讯作者：
Squires, R A
立克次体表面蛋白 Adr2 在 C3H/HeN 小鼠中诱导针对落基山斑疹热的保护性免疫。
影响因子：
5.5
作者：
Gong, Wenping;Xiong, Xiaolu;Wen, Bohai
通讯作者：
Wen, Bohai
影响因子：
3.2
作者：
Kumagai, Yumi;Huang, Haibin;Rikihisa, Yasuko
通讯作者：
Rikihisa, Yasuko
影响因子：
5.2
作者：
Lin M;Kikuchi T;Brewer HM;Norbeck AD;Rikihisa Y
通讯作者：
Rikihisa Y