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Development of a Novel Virus-Like Particle Vaccine Platform That Mimics the Immature Form of Alphavirus

Development of a Novel Virus-Like Particle Vaccine Platform That Mimics the Immature Form of... Development of a Novel Virus-Like Particle Vaccine Platform That Mimics the Immature Form of Alphavirus Akane Urakami a , Atsuko Sakurai a , Momoko Ishikawa a * , Moh Lan Yap b , Yevel Flores-Garcia c , Yasunari Haseda d , Taiki Aoshi d , Fidel P. Zavala c , Michael G. Rossmann b , Sachiko Kuno a , Ryuji Ueno a and Wataru Akahata a a VLP Therapeutics, Gaithersburg, Maryland, USA b Department of Biological Sciences, Purdue University, West Lafayette, Indiana, USA c Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA d Vaccine Dynamics Project, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan Herman F. Staats , Editor Duke University Medical Center 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 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Clinical and Vaccine Immunology American Society For Microbiology

Development of a Novel Virus-Like Particle Vaccine Platform That Mimics the Immature Form of Alphavirus

Clinical and Vaccine Immunology , Volume 24 (7): e00090-17 – Jul 1, 2017

Abstract

Development of a Novel Virus-Like Particle Vaccine Platform That Mimics the Immature Form of Alphavirus Akane Urakami a , Atsuko Sakurai a , Momoko Ishikawa a * , Moh Lan Yap b , Yevel Flores-Garcia c , Yasunari Haseda d , Taiki Aoshi d , Fidel P. Zavala c , Michael G. Rossmann b , Sachiko Kuno a , Ryuji Ueno a and Wataru Akahata a a VLP Therapeutics, Gaithersburg, Maryland, USA b Department of Biological Sciences, Purdue University, West Lafayette, Indiana, USA c Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA d Vaccine Dynamics Project, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan Herman F. Staats , Editor Duke University Medical Center 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

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References (101)

Publisher
American Society For Microbiology
Copyright
Copyright © 2017 by the American society for Microbiology.
ISSN
1556-6811
eISSN
1556-679X
DOI
10.1128/CVI.00090-17
pmid
28515133
Publisher site
See Article on Publisher Site

Abstract

Development of a Novel Virus-Like Particle Vaccine Platform That Mimics the Immature Form of Alphavirus Akane Urakami a , Atsuko Sakurai a , Momoko Ishikawa a * , Moh Lan Yap b , Yevel Flores-Garcia c , Yasunari Haseda d , Taiki Aoshi d , Fidel P. Zavala c , Michael G. Rossmann b , Sachiko Kuno a , Ryuji Ueno a and Wataru Akahata a a VLP Therapeutics, Gaithersburg, Maryland, USA b Department of Biological Sciences, Purdue University, West Lafayette, Indiana, USA c Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA d Vaccine Dynamics Project, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan Herman F. Staats , Editor Duke University Medical Center 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

Journal

Clinical and Vaccine ImmunologyAmerican Society For Microbiology

Published: Jul 1, 2017

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