IMMUNOGENICITY OF RECOMBINANT YF17D-LASSA VACCINE IN COMMON MARMOSETS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 在病毒性出血热的病原体中，拉沙（LAS）和黄热病（YF）病毒影响非洲最多的人。没有拉沙热（LF）的疫苗（3）。相比之下，自1936年以来，YF 17 D减毒活疫苗可用于人类免疫。然而，这种疫苗的可用性差代表了公共卫生政策的失败（5）。于是，YF在非洲重新崛起，出现在南美洲。LF和YF的二价疫苗的可用性可能会产生额外的激励，以增加疫苗的生产，在非洲重叠的流行区域内分发。 YF 17 D的全长感染性cDNA克隆已被用作载体，以设计将LAS病毒糖蛋白表达到感染细胞中的重组YF 17 D/LAS疫苗（1）。重组病毒具有复制能力，可诱导抗YF的抗体，并保护豚鼠免受致死性LF的侵害（1）。该子项目的目标是扩展我们在灵长类动物中的LF研究（2），并检验YF 17 D/LAS疫苗将具有高度免疫原性并在绒猴中诱导保护性免疫应答的假设。具体目标是：1）免疫原性;检验YF 17 D/LAS免疫将刺激LAS和YF特异性免疫应答的假设; 2）效力;检验YF 17 D/LAS免疫接种的动物将被保护免受LAS攻击的假设。

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. Among causative agents of viral hemorrhagic fevers, Lassa (LAS) and Yellow Fever (YF) viruses affect the largest number of people in Africa. There is no vaccine available for Lassa Fever (LF) (3). In contrast, a live attenuated YF17D vaccine was available for human immunization since 1936. However, the poor availability of this vaccine represents a failure of public health policy (5). As a result, YF re-emerged in Africa and appeared in South America. The availability of a bivalent vaccine for both LF and YF may generate additional incentive for increase production of a vaccine to distribute within overlapping endemic regions of Africa. A full-length infectious cDNA clone of the YF17D has been used as a vector to design recombinant YF17D/LAS vaccine expressing LAS virus glycoproteins into infected cells (1). The recombinant virus was replication competent, induced antibodies against YF, and protected guinea pigs against fatal LF (1). The goal of this subproject is to extend our LF studies in primates (2) and to test the hypothesis that the YF17D/LAS vaccine will be highly immunogenic and induce protective immune responses in marmosets. Specific aims are: 1) immunogenicity; test the hypothesis that YF17D/LAS immunization will stimulate LAS- and YF-specific immune responses; 2) efficacy; test the hypothesis that YF17D/LAS-vaccinated animals will be protected against LAS challenge.