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Nat Med. 2016 Dec 19. doi: 10.1038/nm.4253. [Epub ahead of print]

A chikungunya fever vaccine utilizing an insect-specific virus platform.

Author information

  • 1Institute for Translational Science, University of Texas Medical Branch, Galveston, Texas, USA.
  • 2Institute of Human Infections and Immunity, and Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas, USA.
  • 3Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
  • 4National 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.
  • 5Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
  • 6Virology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA.
  • 7Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.

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.

PMID:
27991917
DOI:
10.1038/nm.4253
[PubMed - as supplied by publisher]
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