Vaccine Research Center, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, Maryland, USA.
Nat Med. 2010 Mar;16(3):334-8. doi: 10.1038/nm.2105. Epub 2010 Jan 28.
Chikungunya virus (CHIKV) has infected millions of people in Africa, Europe and Asia since this alphavirus reemerged from Kenya in 2004. The severity of the disease and the spread of this epidemic virus present a serious public health threat in the absence of vaccines or antiviral therapies. Here, we describe a new vaccine that protects against CHIKV infection of nonhuman primates. We show that selective expression of viral structural proteins gives rise to virus-like particles (VLPs) in vitro that resemble replication-competent alphaviruses. Immunization with these VLPs elicited neutralizing antibodies against envelope proteins from alternative CHIKV strains. Monkeys immunized with VLPs produced high-titer neutralizing antibodies that protected against viremia after high-dose challenge. We transferred these antibodies into immunodeficient mice, where they protected against subsequent lethal CHIKV challenge, indicating a humoral mechanism of protection. Immunization with alphavirus VLP vaccines represents a strategy to contain the spread of CHIKV and related pathogenic viruses in humans.
基孔肯雅病毒(CHIKV)自 2004 年从肯尼亚重新出现以来,已在非洲、欧洲和亚洲感染了数百万人。在没有疫苗或抗病毒疗法的情况下,这种流行病毒的疾病严重程度和传播对公共卫生构成了严重威胁。在这里,我们描述了一种可预防非人类灵长类动物感染 CHIKV 的新型疫苗。我们发现,病毒结构蛋白的选择性表达会在体外产生类似于具有复制能力的甲病毒的病毒样颗粒(VLPs)。用这些 VLPs 免疫可诱导针对替代 CHIKV 株包膜蛋白的中和抗体。用 VLPs 免疫的猴子产生了高滴度的中和抗体,可在高剂量攻毒后防止病毒血症。我们将这些抗体转移到免疫缺陷小鼠中,它们可防止随后的致命 CHIKV 攻毒,表明存在体液保护机制。用甲病毒 VLP 疫苗免疫代表了一种控制 CHIKV 和相关致病性病毒在人类中传播的策略。