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Rhodococcus equi: VapA-specific immune responses in adult horses and DNA immunized foals.

机译:马红球菌:成年马和DNA免疫小马驹的VapA特异性免疫反应。

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摘要

Rhodococcus equi remains one of the most important pathogens early in life in horses, yet vaccines against rhodococcal pneumonia have not been successful so far. Since immunocompetent adult horses are not susceptible to R. equi disease, in this study our goals were first, to understand the protective immune response against R. equi in adult horses and second, to develop a vaccine that induces that protective phenotype in the foal.; To characterize the correlates of protection, twelve adult horses were challenged with virulent R. equi. Bronchoalveolar lavage fluid (BALF) cells stimulated with either R. equi or the vaccine candidate VapA resulted in significant proliferation and a significant increase in IFN-γ expression by day 7 post-challenge. Anamnestic increases in all examined IgG antibody isotypes (IgGa, IgGb, IgG(T)) binding R. equi and VapA were detected post-challenge. Anti-VapA IgGb and anti-R. equi IgGa and IgGb antibodies, the equine IgG isotypes that preferentially opsonize and fix complement, were dramatically enhanced and were the predominant isotypes post-challenge. The antigen-specific proliferation of BALF cells, IFN-γ expression by these cells, and the anamnestic increases in opsonizing IgG isotypes are consistent with stimulation of a memory response in immune adult horses and represent correlates for vaccine development in foals.; We developed a DNA vaccine expressing the vapA gene (pVR1055vapA) that induced VapA-specific immune responses in adult ponies. To determine if pVR1055vapA generated VapA-specific primary immune responses, two-week old foals were vaccinated (day 1) by intranasal and intradermal routes with either pVR1055vapA or the negative control pVR1055vapA_rev. All foals were DNA boosted (day 14) and protein boosted (day 30) with either rVapA (VR1055vapA-vaccinates) or rCAT (control group). At day 45, no antigen-specific antibody responses were detected in the control group. However, VapA-specific IgGb, IgGa and IgM were detected in sera of three foals of the VR1055vapAvaccinated group. Two of these animals also had VapA-specific IgG in BALF. These results indicate that although the DNA vaccine reported needs to be improved, it stimulates antibody isotypes associated with protection and therefore constitutes a promising vaccination system against R. equi infection.
机译: Rhodococcus equi 仍然是马生命早期最重要的病原体之一,但迄今为止,针对红球菌肺炎的疫苗尚未成功。由于具有免疫能力的成年马对 R不敏感。在本研究中,我们的目标是首先了解抗 R的保护性免疫应答。在成年马匹中等价;其次,开发一种在小马驹中诱导该保护性表型的疫苗。为了表征保护的相关性,用毒性的 R对十二匹成年马进行了攻击。等。任一 R刺激的支气管肺泡灌洗液(BALF)细胞。攻击后第7天,等当量或候选疫苗VapA导致明显的增殖和IFN-γ表达的明显增加。攻击后检测到所有结合的 R. equi 和VapA的IgG抗体同种型(IgGa,IgGb,IgG(T))记忆消失。抗VapA IgGb和抗 R。优先调理和固定补体的马IgG同种型,即equal IgGa和IgGb抗体,显着增强,并且是攻击后的主要同种型。 BALF细胞的抗原特异性增殖,这些细胞的IFN-γ表达以及调理性IgG同种型的记忆增强与免疫成年马中记忆反应的刺激相一致,并代表了小马驹疫苗开发的相关性。我们开发了一种表达 vapA 基因(pVR1055 vapA )的DNA疫苗,该基因可诱导成年小马的VapA特异性免疫反应。为了确定pVR1055 vapA 是否产生了VapA特异性的初次免疫反应,通过鼻内和皮内途径用pVR1055 vapA 或阴性的两周龄小马进行了疫苗接种(第1天)。控制pVR1055 vapA _rev。用rVapA(VR1055 vapA -疫苗)或rCAT(对照组)对所有驹进行DNA增强(第14天)和蛋白质增强(第30天)。在第45天,对照组中未检测到抗原特异性抗体应答。但是,在接种了VR1055 vapA 疫苗的三只小马驹的血清中检测到了VapA特异性IgGb,IgGa和IgM。这些动物中的两只在BALF中也具有VapA特异性IgG。这些结果表明,尽管报告的DNA疫苗需要改进,但它刺激与保护作用有关的抗体同种型,因此构成了针对 R的有希望的疫苗接种系统。等同感染。

著录项

  • 作者

    Lopez, Alicia Marianela.;

  • 作者单位

    Washington State University.;

  • 授予单位 Washington State University.;
  • 学科 Biology Veterinary Science.; Biology Microbiology.
  • 学位 Ph.D.
  • 年度 2002
  • 页码 64 p.
  • 总页数 64
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 动物学;微生物学;
  • 关键词

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