Development of a novel virus-like particle vaccine platform that mimics the immature form of alphavirus

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere00090-17
JournalClinical and Vaccine Immunology
Volume24
Issue number7
DOIs
Publication statusPublished - Jul 1 2017

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Keywords

  • Alphavirus
  • Chikungunya virus
  • Malaria
  • Vaccines
  • Virus-like particle

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Clinical Biochemistry
  • Microbiology (medical)

Cite this

Urakami, A., Sakurai, A., Ishikawa, M., Yap, M. L., Flores-Garcia, Y., Haseda, Y., ... Akahata, W. (2017). Development of a novel virus-like particle vaccine platform that mimics the immature form of alphavirus. Clinical and Vaccine Immunology, 24(7), [e00090-17]. https://doi.org/10.1128/CVI.00090-17