Research press release


Nature Immunology

Breaking Dengue fever



Gavin Screatonたちは、デングウイルスに感染している患者から多数の抗デングウイルスモノクローナル抗体を得て解析した。そして、ウイルス中和効率の非常に高い新しいタイプの抗体群を発見した。この抗体群が結合するのは、新たに発見されたエピトープ(抗体が認識して結合する特有の構造)で、4種類すべてのDENVのエンベロープに存在する。実験室での試験で、このエピトープを認識できる抗体が、昆虫細胞、ヒト細胞のどちらが作ったウイルスでも効率よく中和することが明らかになった。この発見によって、強力で広い中和能力を持つ抗体の開発が実現可能な今後のワクチン開発の目標となり、また、DENVに共通に使える万能ワクチンへの道が開かれた。

A major new class of highly potent and broadly reactive antibodies, which are capable of neutralizing Dengue Virus (DENV), is reported online this week in Nature Immunology. This is the first reported incidence of an antibody that is capable of neutralising all four forms of the virus, including the form present in mosquitoes, and may lead to the development of effective vaccines and treatments for the disease.

Dengue is a rapidly emerging mosquito borne viral infection with an estimated 400 million infections annually. Geographical spread of DENV continues to widen, threatening the Southern United States and Australia, and there is also concern of possible spread to Southern Europe. Infection with one form of the virus leads to life-long protection against that specific form but not against others. In addition, antibody recognition of virus particles is complicated by dramatic changes in the shell of the virus during its lifecycle. There is therefore an urgent need to understand the human immune response to naturally acquired DENV infection and the response following vaccination.

Gavin Screaton and colleagues analysed a large panel of anti-dengue monoclonal antibodies from human patients who were infected with the virus at the time. They found a new class of antibodies that are highly effective at neutralising the virus, which bind to a newly discovered epitope (a unique structure that antibodies can recognise and bind to) that is present in the envelope of all forms of DENV. In lab tests they find that antibodies capable of recognising this structure can efficiently neutralize viruses produced in both insect and human cells. This discovery makes the development of potent and broadly neutralizing antibodies a realistic goal for future vaccines and may also pave the way for a universal DENV vaccine.

doi: 10.1038/ni.3058

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