Preclinical Studies of Bunyaviruses

由节肢动物传播的布尼亚病毒科成员被认为是全世界疾病的主要原因。裂谷热病毒(RVFV)在非洲地区的流行性暴发已导致人类和家畜患上严重疾病。虽然最初仅限于非洲，但RVFV已蔓延到中东，并对其他区域构成风险。目前还没有获得许可的疫苗来预防人类裂谷热，尽管有两种灭活疫苗在动物中的使用有限。 疫苗开发：在我们努力为BunyaVirus组创造活体减毒病毒候选疫苗的过程中，我们之前制造了表达詹姆斯敦峡谷病毒附着糖蛋白的重组La Crosse病毒。JCV/LACV嵌合病毒包括来源于LACV的S和L片段和一个嵌合的M片段，其中LACV的ORF被JCV的ORF替换，其两侧是LACV的非编码区。这项研究的结果于2012年发表。虽然我们目前没有计划进一步评估加州脑炎病毒的候选疫苗，但利用LACV遗传背景来传递致病性布尼亚病毒(如RVFV)的M段保护性抗原，可能是快速开发用于人类和动物的减毒活疫苗的有效方法。LACV-RVFV嵌合方法的一个重要好处是能够从血清学上区分RVFV疫苗接种的动物和自然感染的动物，因为接种疫苗的动物也会有针对LACV蛋白的可检测抗体。我们已经构建了表达RVFV糖蛋白的LACV M片段的嵌合cDNA克隆。该嵌合片段目前正与LACV S和L片段一起用于产生重组病毒。

Arthropod-borne members of the family Bunyaviridae are recognized as major causes of disease throughout the World. Epizootic outbreaks of Rift Valley fever virus (RVFV) in regions of Africa have resulted in severe disease in humans and domestic animals. Although initially confined to Africa, RVFV has spread to the Middle East and constitutes a risk to other regions. There are currently no licensed vaccines for preventing Rift Valley fever in people, although there are 2 inactivated vaccines with limited use in animals. Vaccine development: In our efforts to create live-attenuated viral vaccine candidates for the bunyavirus group, we previously generated a recombinant La Crosse virus expressing the attachment glycoproteins of Jamestown Canyon virus. The JCV/LACV chimeric virus contains full-length S and L segments derived from LACV and a chimeric M segment in which the ORF of LACV is replaced with that derived from JCV and is flanked by the non-coding regions of LACV. The results of this research were published in 2012. Although we do not currently have plans to further evaluate vaccine candidates for the California encephalitis viruses, the use of the LACV genetic background to deliver M segment protective antigens from pathogenic bunyaviruses, such as RVFV, could be an efficient method for the rapid development of live attenuated vaccines for use in humans and animals. An important benefit of the LACV-RVFV chimeric approach would be the ability to serologically distinguish RVFV-vaccinated animals from naturally-infected animals since vaccinated animals would also have detectable antibodies to LACV proteins. We have created several chimeric cDNA clones of the LACV M segment expressing the glycoprotein of RVFV. This chimeric segment is currently being used with the LACV S and L segments to generate recombinant virus.