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; 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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 新颖的F. hepatica ag最近被克隆和表征。它是F. hepatica saposin样蛋白家族的成员，该家族在感染的早期阶段由寄生虫表达，当它注入兔子时会引起对挑战感染的强烈抗性。先前在小鼠中的免疫研究表明，FHSAP-2诱导混合的Th1/Th2反应，当作为DNA疫苗传递时，该反应略微极化为Th1。已经证明，在慢性筋膜病中，感染与Th2反应有关。然而，在动物中，已经观察到对感染的天然抗性高水平的IgG2和Th1型反应的IFNG特征。因此，TH1反应似乎对于诱导感染的抗性是必不可少的。从我们组获得的先前结果表明，FHSAP-2是fasciola/scistosoma交叉反应抗原。由于两种物种之间的异源免疫力已被证明，FHSAP-2可能可能构成针对两种疾病的多组分疫苗的一部分。因此，FHSAP-2已成为一种新型有希望的疫苗候选者，这也可能构成双脂肪菌/血吸虫疫苗的基础。在开始进行大型疫苗接种试验之前，需要进行其他初步结果。我们先前证明，FHSAP-2可引起对受到挑战感染的重大保护。但是，在这项研究中，我们无法确定该保护是偏见还是偏向于Th2。在小鼠研究中，我们评估了用FHSAP-2免疫后的免疫反应，并表明Th1偏置反应可能是主要的，但未能确定该免疫方案是否授予任何保护。我们还证明了FHSAP-2是fasciola/sustosoma交叉反应性AG。但是，简单的交叉反应性不应该是开发针对血吸虫病的疫苗的唯一标准。当前的提案旨在实现两个具体目标。在AIM1中，我们将表征小鼠产生的FHSAP-2的免疫反应，我们将确定该保护是偏见还是偏向于Th2。在AIM-2中，我们将确定用辐照cercariae免疫的小鼠的血清（血吸虫病的金标准疫苗）是否识别FHSAP-2，以及同源性FHSAP-2是否在S. Mansoni中退出。在本试点项目中获得的结果将在短时间内提交RO1项目。