ACTIVITY 6 - HUMORAL/CELLULAR RESPONSE IN MICE - FHEPATICA VACCINE CANDIDATE

活动 6 - 小鼠的体液/细胞反应 - FHEPATICA 候选疫苗

• 批准号: 7561542
• 负责人: ANA M ESPINO
• 金额: $ 10.83万
• 依托单位: UNIVERSITY OF PUERTO RICO MED SCIENCES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7561542
• 关键词: Animals; Antigens; Characteristics; Chronic; Computer Retrieval of Information on Scientific Projects Database; DNA Vaccines; Disease; Fasciola; Fascioliasis; Funding; Gold; Grant; Hepatica; Homologous Gene; IgG2; Immune response; Immunity; Immunization; Infection; Institution; Mus; Natural Resistance; Oryctolagus cuniculus; Parasites; Pilot Projects; Protein Family; Protocols documentation; Research; Research Personnel; Resistance; Resistance to infection; Resources; Saposins; Schistosoma; Schistosoma mansoni; Schistosomiasis; Serum; Source; Staging; Standards of Weights and Measures; Time; United States National Institutes of Health; Vaccination; Vaccines; base; cross reactivity; member; novel; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A novel F. hepatica Ag was recently cloned and characterized. It is a member of the F. hepatica saposin-like protein family which is expressed by parasite at early stages of infection and when it is injected in rabbits induce a strong resistance to a challenge infection. Previous immunization studies in mice have revealed that FhSAP-2 induce a mixed Th1/Th2 response, which is slightly polarized to Th1 when is delivered as DNA vaccine. It has been demonstrated that in chronic fascioliasis the infection is associated to Th2 response. However, in animals than develop a natural resistance to infection high levels of IgG2 and IFNg characteristic of a Th1 type response have been observed. Thus, the Th1 response appears to be necessary for inducing resistance to infection. A previous result obtained from our group suggests that FhSAP-2 is a Fasciola/Schistosoma cross-reactive antigen. Because of the heterologous immunity between both species has been demonstrated it is possible that FhSAP-2 could form part of a multi-component vaccine against both diseases. Thus, FhSAP-2 has become in a novel promising vaccine candidate that could also constitute the base for a dual-Fasciola/Schistosoma vaccine. Additional preliminary results need to be compiled before to initiate large vaccination trials. We previously demonstrated that FhSAP-2 induces significant protection against a challenged infection. However, in that study we failed to determine whether this protection is Th1-biased or Th2-biased. In the mouse study we evaluated the immune response after immunization with FhSAP-2 and showed that Th1-biased response may be predominant, but failed to determine whether this immunization protocol conferred any protection. We also demonstrated that FhSAP-2 is a Fasciola/Schistosoma cross-reactive Ag. However, the simple cross-reactivity should not be the only criterion for developing a vaccine against schistosomiasis. The current proposal intends to accomplish two specific aims. In the Aim1 we will characterize the immune responses to FhSAP-2 produced in mice and we will determine if this protection is Th1-biased or Th2-biased. In the Aim-2 we will determine whether sera from mouse immunized with irradiated cercariae (the gold standard vaccine for schistosomiasis) recognize FhSAP-2 and whether a homolog FhSAP-2 exits in S. mansoni. The results to be obtained in the present pilot project will serve to submit an RO1 project in short period of time.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 最近克隆并鉴定了一种新型肝片杆菌Ag。它是肝镰孢皂苷样蛋白家族的成员，该蛋白在感染早期由寄生虫表达，当将其注射到兔子体内时，可诱导对攻击感染的强大抵抗力。先前的小鼠免疫研究表明，FhSAP-2 诱导混合 Th1/Th2 反应，当作为 DNA 疫苗递送时，该反应略微极化为 Th1。已经证明，慢性片形吸虫病的感染与 Th2 反应相关。然而，在动物中观察到对感染产生天然抵抗力的高水平 IgG2 和 IFNg，这是 Th1 型反应的特征。因此，Th1 反应似乎对于诱导感染抵抗力是必要的。我们小组先前获得的结果表明 FhSAP-2 是一种片形吸虫/血吸虫交叉反应抗原。由于两个物种之间的异源免疫已被证明，FhSAP-2 有可能成为针对这两种疾病的多组分疫苗的一部分。因此，FhSAP-2 已成为一种新型有前途的候选疫苗，也可以构成片形吸虫/血吸虫双重疫苗的基础。在启动大型疫苗接种试验之前，需要收集额外的初步结果。我们之前证明 FhSAP-2 可针对挑战性感染产生显着的保护作用。然而，在那项研究中，我们未能确定这种保护是偏向 Th1 还是偏向 Th2。在小鼠研究中，我们评估了 FhSAP-2 免疫后的免疫反应，结果表明 Th1 偏向反应可能占主导地位，但未能确定该免疫方案是否能提供任何保护。我们还证明了 FhSAP-2 是一种片形吸虫/血吸虫交叉反应性抗原。然而，简单的交叉反应不应成为开发血吸虫病疫苗的唯一标准。当前的提案旨在实现两个具体目标。在 Aim1 中，我们将描述小鼠体内产生的对 FhSAP-2 的免疫反应，并确定这种保护是 Th1 偏向的还是 Th2 偏向的。在 Aim-2 中，我们将确定用辐射尾蚴（血吸虫病金标准疫苗）免疫的小鼠血清是否识别 FhSAP-2，以及曼氏血吸虫中是否存在同源 FhSAP-2。目前试点项目取得的结果将有助于在短时间内提交RO1项目。