A chikungunya fever vaccine utilizing an insect-specific virus platform

Jesse H. Erasmus, Albert J. Auguste, Jason T. Kaelber, Huanle Luo, Shannan L. Rossi, Karla Fenton, Grace Leal, Dal Y. Kim, Wah Chiu, Tian Wang, Ilya Frolov, Farooq Nasar, Scott C. Weaver

Research output: Contribution to journalArticle

48 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)192-199
Number of pages8
JournalNature Medicine
Volume23
Issue number2
DOIs
StatePublished - Feb 1 2017

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Erasmus, J. H., Auguste, A. J., Kaelber, J. T., Luo, H., Rossi, S. L., Fenton, K., Leal, G., Kim, D. Y., Chiu, W., Wang, T., Frolov, I., Nasar, F., & Weaver, S. C. (2017). A chikungunya fever vaccine utilizing an insect-specific virus platform. Nature Medicine, 23(2), 192-199. https://doi.org/10.1038/nm.4253