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接种 LetiFend® 可降低实验感染利什曼原虫犬的循环免疫复合物。

Vaccination with LetiFend® reduces circulating immune complexes in dogs experimentally infected with L. infantum.

机构信息

R&D Unit. Allergy & Immunology. Laboratorios LETI S.L., Tres Cantos, Madrid, Spain.

Centro de Biología Molecular Severo Ochoa, CSIC-Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain.

出版信息

Vaccine. 2020 Jan 22;38(4):890-896. doi: 10.1016/j.vaccine.2019.10.078. Epub 2019 Nov 6.

Abstract

Domestic dogs constitute the main reservoir of Leishmania infantum and play a key role in transmission to humans. The main tool for controlling infection spread is a safe and effective vaccine, as successful immunization of dogs could significantly reduce the incidence of human visceral leishmaniosis (VL) and is the most cost-effective control strategy. The factors that determine disease progression in canine leishmaniosis (CanL) remain poorly understood, though a previous study in naturally infected dogs has demonstrated a clear relationship between the presence of circulating immune complexes (CIC) in the blood and disease progression. Thus, the aim of this study was to compare CIC levels in serum samples from dogs vaccinated or unvaccinated with LetiFend®, a new vaccine containing recombinant Protein Q, and experimentally infected with L. infantum. CIC were isolated from vaccinated or unvaccinated dogs after experimental infection with L. infantum and their levels measured by ELISA. Furthermore, reverse phase-liquid chromatography-mass spectrometry (RP-LC-MS/MS) analysis was used to investigate the protein composition of precipitated CIC. At all the time points analyzed after infection, the amount of CIC was lower in the vaccinated group compared to the placebo group. Furthermore, there were differences in the protein composition of precipitated CIC between the vaccinated and unvaccinated groups. In conclusion, administration of LetiFend® was able to reduce CIC elicited after experimental infection with L. infantum in a dog model in a process that may be related to complement system activation.

摘要

家犬是利什曼原虫的主要宿主,在向人类传播中起着关键作用。控制感染传播的主要工具是安全有效的疫苗,因为犬类的成功免疫可以显著降低人类内脏利什曼病(VL)的发病率,是最具成本效益的控制策略。尽管之前在自然感染的犬中进行的一项研究表明,血液中循环免疫复合物(CIC)的存在与疾病进展之间存在明确关系,但犬利什曼病(CanL)进展的决定因素仍知之甚少。因此,本研究旨在比较接种或未接种含有重组蛋白 Q 的新型疫苗 LetiFend®的犬血清样本中的 CIC 水平,这些犬经过实验性感染利什曼原虫。在实验性感染利什曼原虫后,从接种或未接种疫苗的犬中分离 CIC,并通过 ELISA 测量其水平。此外,还使用反相液相色谱-质谱联用(RP-LC-MS/MS)分析来研究沉淀 CIC 的蛋白组成。在感染后分析的所有时间点,接种组的 CIC 量均低于安慰剂组。此外,在接种组和未接种组之间,沉淀 CIC 的蛋白组成存在差异。总之,在犬模型中,LetiFend®的给药能够降低实验性感染利什曼原虫后 CIC 的产生,这一过程可能与补体系统的激活有关。

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