A chikungunya fever vaccine utilizing an insect-specific virus platform

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

Research output: Contribution to journalArticle

37 Citations (Scopus)

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

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Insect Viruses
Viruses
Chikungunya virus
Vaccines
Safety
Inactivated Vaccines
Immunity
Alphavirus
Viral Structural Proteins
Cryoelectron Microscopy
Chikungunya Fever
Attenuated Vaccines
Viremia
Viral RNA
Pandemics
Virus Replication
Neutralizing Antibodies
Culicidae
Primates
Insects

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Erasmus, J. H., Auguste, A. J., Kaelber, J. T., Luo, H., Rossi, S., Fenton, K., ... Weaver, S. (2017). A chikungunya fever vaccine utilizing an insect-specific virus platform. Nature Medicine, 23(2), 192-199. https://doi.org/10.1038/nm.4253

A chikungunya fever vaccine utilizing an insect-specific virus platform. / Erasmus, Jesse H.; Auguste, Albert J.; Kaelber, Jason T.; Luo, Huanle; Rossi, Shannan; Fenton, Karla; Leal, Grace; Kim, Dal Y.; Chiu, Wah; Wang, Tian; Frolov, Ilya; Nasar, Farooq; Weaver, Scott.

In: Nature Medicine, Vol. 23, No. 2, 01.02.2017, p. 192-199.

Research output: Contribution to journalArticle

Erasmus, JH, Auguste, AJ, Kaelber, JT, Luo, H, Rossi, S, Fenton, K, Leal, G, Kim, DY, Chiu, W, Wang, T, Frolov, I, Nasar, F & Weaver, S 2017, 'A chikungunya fever vaccine utilizing an insect-specific virus platform', Nature Medicine, vol. 23, no. 2, pp. 192-199. https://doi.org/10.1038/nm.4253
Erasmus JH, Auguste AJ, Kaelber JT, Luo H, Rossi S, Fenton K et al. A chikungunya fever vaccine utilizing an insect-specific virus platform. Nature Medicine. 2017 Feb 1;23(2):192-199. https://doi.org/10.1038/nm.4253
Erasmus, Jesse H. ; Auguste, Albert J. ; Kaelber, Jason T. ; Luo, Huanle ; Rossi, Shannan ; Fenton, Karla ; Leal, Grace ; Kim, Dal Y. ; Chiu, Wah ; Wang, Tian ; Frolov, Ilya ; Nasar, Farooq ; Weaver, Scott. / A chikungunya fever vaccine utilizing an insect-specific virus platform. In: Nature Medicine. 2017 ; Vol. 23, No. 2. pp. 192-199.
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