Ehrlichia chaffeensis is an obligatory intracellular bacterium that causes human monocytic ehrlichiosis, an emerging disease transmitted by the Lone Star tick, Amblyomma americanum. E. chaffeensis outer membrane protein entry triggering protein of Ehrlichia (EtpE) is necessary for bacterial entry into human cells. We investigated the role of EtpE in transmission of the bacteria from tick to human cells and whether or not vaccination with EtpE can prevent transmission of ehrlichiae from ticks to mammals. An antiserum against the recombinant C terminus of EtpE (rEtpE-C), which binds a mammalian cell-surface receptor and triggers bacterial entry, significantly inhibited E. chaffeensis transmission from infected tick cells to human monocytes in culture. Each of five specific-pathogen-free dogs were vaccinated with rEtpE-C along with an immunostimulating complex or were sham vaccinated with the complex alone. Dogs vaccinated with rEtpE-C developed high antibody titers against rEtpE-C and produced interferon-γ-secreting cells, as assessed with the ELISpot assay. All 10 dogs were challenged with A. americanum adult ticks infected as nymphs by syringe inoculation with E. chaffeensis. Upon challenge, both the vaccinated and control dogs became infected by day 1 post-tick attachment, but the majority of rEtpE-C-vaccinated dogs rapidly cleared the infection from the bloodstream as soon as day 7, whereas most of sham-vaccinated dogs remained infected at day 35. Peripheral blood leukocytes from vaccinated dogs had significantly elevated interferon-γ mRNA levels and secreted significantly elevated interferon-γ soon after tick attachment. Thus, the EtpE-C vaccine represents the first ehrlichial protein vaccine demonstrated to reduce bacterial infection in mammals upon challenge with infected ticks.

中文翻译：

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埃立克体的一种进入触发蛋白是一种新的候选疫苗，可对抗蜱传人单核细胞埃立克体病。

Ehrlichia chaffeensis是一种强制性的细胞内细菌，可导致人类单核细胞埃立克体病，这是一种由孤星蜱、美洲钝缘蜱传播的新兴疾病。E. chaffeensis 埃立克体外膜蛋白进入触发蛋白( EtpE ) 是细菌进入人体细胞所必需的。我们研究了 EtpE 在细菌从蜱传播到人体细胞中的作用，以及接种 EtpE 是否可以防止埃立克体从蜱传播到哺乳动物。针对 EtpE 的重组 C 末端 (rEtpE-C) 的抗血清可与哺乳动物细胞表面受体结合并触发细菌进入，显着抑制E. chaffeensis从受感染的蜱细胞传播到培养物中的人单核细胞。五只无特定病原体的狗中的每只都接种了 rEtpE-C 和免疫刺激复合物，或者只接种了复合物假疫苗。用 ELISpot 测定法评估，接种 rEtpE-C 的狗产生了针对 rEtpE-C 的高抗体滴度并产生了干扰素-γ-分泌细胞。所有 10 只狗都通过注射器接种 E.chaffeensis 以作为若虫感染的A. Americanum成年蜱进行攻击. 在攻击后，接种疫苗和对照狗在蜱附着后的第 1 天都被感染，但大多数接种 rEtpE-C 的狗在第 7 天就迅速从血液中清除了感染，而大多数假疫苗接种的狗仍然存在在第 35 天感染。接种犬的外周血白细胞具有显着升高的干扰素-γ mRNA 水平，并在蜱附着后不久分泌显着升高的干扰素-γ。因此，EtpE-C 疫苗代表了第一个埃里希体蛋白疫苗，该疫苗被证明可以减少哺乳动物在受到感染蜱的攻击时的细菌感染。