嵌合型基孔肯雅病毒在高度敏感的小鼠模型中无致病性，但能有效诱导保护性免疫反应。
Chimeric Chikungunya viruses are nonpathogenic in highly sensitive mouse models but efficiently induce a protective immune response.
机构信息
Institute for Human Infections and Immunity, Sealy Center for Vaccine Development, and Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
出版信息
J Virol. 2011 Sep;85(17):9249-52. doi: 10.1128/JVI.00844-11. Epub 2011 Jun 22.
Abstract
Chikungunya virus (CHIKV) is an important pathogen causing outbreaks of highly debilitating and often chronic, arthralgic human disease. We have designed chimeric alphaviruses encoding CHIKV-specific structural proteins but no structural or nonstructural proteins capable of interfering with development of cellular antiviral response. These chimeras demonstrate a highly attenuated phenotype in both immunocompetent and immunocompromised (A129) mice. However, after a single vaccination, they induced protective immune response against subsequent CHIKV challenge, characterized by high titers of neutralizing antibodies. The rational design of alphavirus genomes provides a strong basis for the development of new recombinant alphaviruses with irreversible, highly attenuated, cell type-restricted phenotypes.
摘要
基孔肯雅病毒（CHIKV）是一种重要的病原体，可引起高度虚弱且常常慢性关节痛的人类疾病爆发。我们设计了嵌合甲病毒，其编码 CHIKV 特异性结构蛋白，但没有能够干扰细胞抗病毒反应发展的结构或非结构蛋白。这些嵌合体在免疫功能正常和免疫功能低下（A129）的小鼠中均表现出高度减毒的表型。然而，单次接种后，它们诱导了针对随后的 CHIKV 挑战的保护性免疫应答，其特征是中和抗体的高滴度。甲病毒基因组的合理设计为开发具有不可逆、高度减毒、细胞类型受限表型的新型重组甲病毒提供了坚实的基础。
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