title: A chikungunya fever vaccine utilizing an insect-specific virus platform.
abstract: Traditionally, vaccine development involves tradeoffs between immunogenicity and safety. Live-attenuated vaccines typically offer rapid and durable immunity but have reduced safety when compared to inactivated vaccines. In contrast, the inability of inactivated vaccines to replicate enhances safety at the expense of immunogenicity, often necessitating multiple doses and boosters. To overcome these tradeoffs, we developed the insect-specific alphavirus, Eilat virus (EILV), as a vaccine platform. To address the chikungunya fever (CHIKF) pandemic, we used an EILV cDNA clone to design a chimeric virus containing the chikungunya virus (CHIKV) structural proteins. The recombinant EILV/CHIKV was structurally identical at 10 Å to wild-type CHIKV, as determined by single-particle cryo-electron microscopy, and it mimicked the early stages of CHIKV replication in vertebrate cells from attachment and entry to viral RNA delivery. Yet the recombinant virus remained completely defective for productive replication, providing a high degree of safety. A single dose of EILV/CHIKV produced in mosquito cells elicited rapid (within 4 d) and long-lasting (>290 d) neutralizing antibodies that provided complete protection in two different mouse models. In nonhuman primates, EILV/CHIKV elicited rapid and robust immunity that protected against viremia and telemetrically monitored fever. Our EILV platform represents the first structurally native application of an insect-specific virus in preclinical vaccine development and highlights the potential application of such viruses in vaccinology.
authors.affiliation: Institute for Translational Science, University of Texas Medical Branch, Galveston, Texas, USA.|Institute of Human Infections and Immunity, and Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Jesse H
authors.identifier: http://orcid.org/0000-0003-1612-2697
authors.initials: JH
authors.lastname: Erasmus
authors.affiliation: Institute of Human Infections and Immunity, and Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas, USA.|Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Auguste
authors.affiliation: National Center for Macromolecular Imaging, Verna and Marrs McLean Department of Biochemistry and Molecular Biology and Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Jason T
authors.identifier: http://orcid.org/0000-0001-9426-1030
authors.initials: JT
authors.lastname: Kaelber
authors.affiliation: Institute of Human Infections and Immunity, and Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Huanle
authors.initials: H
authors.lastname: Luo
authors.affiliation: Institute of Human Infections and Immunity, and Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas, USA.|Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Shannan L
authors.initials: SL
authors.lastname: Rossi
authors.affiliation: Institute of Human Infections and Immunity, and Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Karla
authors.initials: K
authors.lastname: Fenton
authors.affiliation: Institute of Human Infections and Immunity, and Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Grace
authors.initials: G
authors.lastname: Leal
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Dal Y
authors.initials: DY
authors.lastname: Kim
authors.affiliation: National Center for Macromolecular Imaging, Verna and Marrs McLean Department of Biochemistry and Molecular Biology and Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Wah
authors.initials: W
authors.lastname: Chiu
authors.affiliation: Institute of Human Infections and Immunity, and Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Tian
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Ilya
authors.initials: I
authors.lastname: Frolov
authors.affiliation: Virology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA.
authors.forename: Farooq
authors.initials: F
authors.lastname: Nasar
authors.affiliation: Institute for Translational Science, University of Texas Medical Branch, Galveston, Texas, USA.|Institute of Human Infections and Immunity, and Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas, USA.|Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.|Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Scott C
authors.initials: SC
authors.lastname: Weaver
mesh_terms: D000524:Alphavirus / Q000276:immunology* / Q000648:ultrastructure; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D002460:Cell Line; D065632:Chikungunya Fever / Q000517:prevention & control*; D002646:Chikungunya virus / Q000276:immunology* / Q000648:ultrastructure; D002678:Chimera; D020285:Cryoelectron Microscopy; D009033:Culicidae / Q000821:virology; D005260:Female; D005434:Flow Cytometry; D000071497:Immunogenicity, Vaccine / Q000276:immunology*; D007304:Insect Viruses / Q000276:immunology*; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D014613:Vaccines, Attenuated / Q000276:immunology; D015164:Vaccines, Inactivated / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*; D014779:Virus Replication
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D014613:Vaccines, Attenuated; D015164:Vaccines, Inactivated; D014765:Viral Vaccines