@article{0133ab3e591842baa7d66428726eec2d,
title = "Development of a novel virus-like particle vaccine platform that mimics the immature form of alphavirus",
abstract = "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 in vivo dynamics and enhanced its immunogenicity. We used the circumsporozoite protein (CSP) of the Plasmodium falciparum 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 P. yoelii 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.",
keywords = "Alphavirus, Chikungunya virus, Malaria, Vaccines, Virus-like particle",
author = "Akane Urakami and Atsuko Sakurai and Momoko Ishikawa and Yap, {Moh Lan} and Yevel Flores-Garcia and Yasunari Haseda and Taiki Aoshi and Zavala, {Fidel P.} and Rossmann, {Michael G.} and Sachiko Kuno and Ryuji Ueno and Wataru Akahata",
note = "Funding Information: We thank K. Tolliver, M. Nakata, and S. Mayer (VLP Therapeutics) and E. Cho-Fertikh (ECF Biosolutions) for facilitation of collaborations, manuscript preparation, and helpful discussions. We thank E. Locke and N. Richie (WRAIR) for measuring anti-CSP antibody titer in monkeys. We also thank A. Fokine (Purdue University) for assistance with the cryo-EM data analysis. We gratefully acknowledge H. Anderson (Bioqual) and S. Cherukuri (Noble Life Sciences) for managing animal experiments, Y. Zhang (AscentGene) for lentivirus experiments, R. Schuman (AIC Biotech) for assistance with monoclonal antibody production, and B. Smith (Johns Hopkins University) for EM analysis. This research was funded by VLP Therapeutics and National Institutes of Health through grant R01 AI095366. We declare that an intellectual property application has been filed by VLP Therapeutics based on data presented in this paper. A.U., A.S., and M.I. were employees of VLP Therapeutics at the time of the study. S.K., R.U., and W.A. designed the research and are management members and shareholders of VLP Therapeutics. Publisher Copyright: Copyright {\textcopyright} 2017 American Society for Microbiology. All Rights Reserved.",
year = "2017",
month = jul,
doi = "10.1128/CVI.00090-17",
language = "English (US)",
volume = "24",
journal = "Clinical and Vaccine Immunology",
issn = "1556-6811",
publisher = "American Society for Microbiology",
number = "7",
}