Scientists mutate H5N1 in vaccine search

　　Scientists have mutated a protein of the H5N1 virus to identify changes which could make the virus capable of passing between humans, and create variants that could be used as pre-emptive vaccines.

　　The findings are reported by Yang Zhi-Yong and colleagues in the 10 August issue of Science.

　　The H5N1 virus causes avian influenza, or 'bird flu', which can occasionally be passed to humans. According to the World Health Organization, it has infected more than 300 people worldwide, of whom 192 had died by 25 July this year.

　　So far no human-to-human transmission of the virus has been reported. Scientists believe that for the H5N1 virus to spread among humans, a mutation must occur in the protein spikes on its surface, known as haemagglutinin (HA). The virus enters a host cell after part of HA, the receptor-binding domain (RBD), has bound to a specific part of the cell.

　　Scientists at the United States' National Institute of Allergy and Infectious Diseases (NIAID) created specific mutations in the RBD of H5N1 and then tested the ability of the mutated RBD structure to recognise bird and human cells.

　　Rather than using real H5N1 virus, the researchers altered the RBD of HA protein in artificial forms of the virus –– called pseudoviruses –– which do not cause disease but are otherwise a good model of H5N1.

　　The researchers believe the method can guide the development of vaccines and therapeutic antibodies "that can be evaluated before the emergence of human-adapted H5N1 strains".

　　"There is no guarantee that we will find the precise mutations needed to adapt to human [cells], but we can be prepared for most of them and there are probably a limited number of ways the virus can adapt to recognise the receptor [of human cells]," corresponding author Gary J. Nabel of NIAID told SciDev.Net.

　　He adds that new virus variants made in the study could be used to generate vaccine stocks against possible H5N1 virus mutants.

　　Dong Xiaoping of the Institute of Virology at the Chinese Centre for Disease Control welcomed the study.

　　"The HA protein is the most widely used target for vaccines against H5N1 virus. The method might help vaccines developed through different approaches targeting some common areas in the HA proteins," says Dong, who chairs China's ongoing development of human H5N1 vaccine.

　　"But more studies are needed to test the possible interactions between the identified structural change of the HA protein and the pseudovirus carrying it, as well as the safety issues incurred by the interactions," Dong told SciDev.Net.

　　科学家修改H5N1病毒蛋白，帮助疫苗研究

　　科学家修改了H5N1病毒的一个蛋白，从而使其用于发现哪些突变可能让这种病毒进行人际传播，并创造出能用来制作预先防范性（pre-emptive）疫苗的毒株。

　　美国国立过敏症与传染病研究所(NIAID)的Yang Zhi-Yong及其同事在8月10日出版的《科学》杂志上发表了这项研究。

　　H5N1病毒引发了禽流感，它也能偶然传给人类。据世界卫生组织统计，到今年7月25日，H5N1禽流感病毒已经在全世界感染了300多人，其中192人已经死亡。

　　目前还没有报道H5N1禽流感病毒在人际间传播的病例。科学家相信，如果这种病毒要在人际传播，它表面的一种名为血凝素的刺状蛋白必须发生变异。血凝素蛋白的一个称之为受体结合区(RBD)的部分与宿主细胞的特定部分结合在一起之后，这种病毒才能在进入宿主细胞。

　　NIAID的科学家让H5N1禽流感病毒受体结合区发生了特定变化，然后测试了结构发生变化的受体结合区识别禽类和人体细胞的能力。他们并没有使用真的禽流感病毒，而是在一种人造病毒上改变了血凝素蛋白的受体结合区(RBD)。这种人造病毒被称为假病毒（pseudoviruses），它不会引起疾病，但也能成为H5N1病毒的一个良好模型。

　　科学家相信，这种方法能指导开发疫苗和治疗性抗体，在H5N1禽流感病毒变得适应人际传播之前就可以评估这些疫苗和抗体。

　　论文通讯作者、NIAID疫苗研究中心的主任Gary J. Nabel对本网络记者说：“并不能保证我们会精确地发现H5N1病毒适应人体细胞所需的变异，但是我们能为大多数可能发生的变异做好准备，病毒变异得能识别人体细胞受体的方式可能并不多。”

　　他还说，这项研究中创造的新的病毒毒株可以被用来制造疫苗库存，对付可能的H5N1禽流感病毒变异。

　　中国疾病预防控制中心病毒研究所的董小平领导了中国正在进行临床试验的人用禽流感疫苗项目，他对这项研究表示欢迎，他说：“正在开发的针对H5N1病毒的疫苗中，血凝素蛋白是最常用的靶点。这种方法也许能有助于通过不同方法开发的疫苗在血凝素蛋白上面找到一些通用的靶点，”

　　不过，董小平也告诉本网络记者：“我们还需要更多的研究，来测试被鉴别出来的血凝素蛋白的变异与携带它的假病毒之间可能发生的相互作用，也要认真研究这种相互作用引发的安全性问题。”

　　本文由科学与发展网络(SciDev.Net)独家提供。

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