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-Structure paper
タイトル | Development of a Novel Virus-Like Particle Vaccine Platform That Mimics the Immature Form of Alphavirus. |
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ジャーナル・号・ページ | Clin Vaccine Immunol, Vol. 24, Issue 7, Year 2017 |
掲載日 | 2017年7月5日 |
著者 | Akane Urakami / Atsuko Sakurai / Momoko Ishikawa / Moh Lan Yap / Yevel Flores-Garcia / Yasunari Haseda / Taiki Aoshi / Fidel P Zavala / Michael G Rossmann / Sachiko Kuno / Ryuji Ueno / Wataru Akahata / |
PubMed 要旨 | Virus-like particles (VLPs) are noninfectious multiprotein structures that are engineered to self-assemble from viral structural proteins. Here, we developed a novel VLP-based vaccine platform ...Virus-like particles (VLPs) are noninfectious multiprotein structures that are engineered to self-assemble from viral structural proteins. Here, we developed a novel VLP-based vaccine platform utilizing VLPs from the chikungunya virus. We identified two regions within the envelope protein, a structural component of chikungunya, where foreign antigens can be inserted without compromising VLP structure. Our VLP displays 480 copious copies of an inserted antigen on the VLP surface in a highly symmetric manner and is thus capable of inducing strong immune responses against any inserted antigen. Furthermore, by mimicking the structure of the immature form of the virus, we altered our VLP's dynamics and enhanced its immunogenicity. We used the circumsporozoite protein (CSP) of the malaria parasite as an antigen and demonstrated that our VLP-based vaccine elicits strong immune responses against CSP in animals. The sera from immunized monkeys protected mice from malaria infection. Likewise, mice vaccinated with CSP-containing VLPs were protected from an infectious sporozoite challenge. Hence, our uniquely engineered VLP platform can serve as a blueprint for the development of vaccines against other pathogens and diseases. |
リンク | Clin Vaccine Immunol / PubMed:28515133 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 11.0 - 12.2 Å |
構造データ | EMDB-8424: EMDB-8425: |
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