Novel insect-specific Eilat virus-based chimeric vaccine candidates provide durable, mono- and multivalent, single-dose protection against lethal alphavirus challenge

Jesse H. Erasmus, Robert Seymour, Jason T. Kaelber, Dal Y. Kim, Grace Leal, Michael Sherman, Ilya Frolov, Wah Chiu, Scott Weaver, Farooq Nasar

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Most alphaviruses are mosquito borne and exhibit a broad host range, infecting many different vertebrates, including birds, rodents, equids, humans, and nonhuman primates. Recently, a host-restricted, mosquito-borne alphavirus, Eilat virus (EILV), was described with an inability to infect vertebrate cells based on defective attachment and/or entry, as well as a lack of genomic RNA replication. We investigated the utilization of EILV recombinant technology as a vaccine platform against eastern (EEEV) and Venezuelan equine encephalitis viruses (VEEV), two important pathogens of humans and domesticated animals. EILV chimeras containing structural proteins of EEEV or VEEV were engineered and successfully rescued in Aedes albopictus cells. Cryo-electron microscopy reconstructions at 8 and 11 Å of EILV/VEEV and EILV/EEEV, respectively, showed virion and glycoprotein spike structures similar to those of VEEV-TC83 and other alphaviruses. The chimeras were unable to replicate in vertebrate cell lines or in brains of newborn mice when injected intracranially. Histopathologic examinations of the brain tissues showed no evidence of pathological lesions and were indistinguishable from those of mock-infected animals. A single-dose immunization of either monovalent or multivalent EILV chimera( s) generated neutralizing antibody responses and protected animals against lethal challenge 70 days later. Lastly, a single dose of monovalent EILV chimeras generated protective responses as early as day 1 postvaccination and partial or complete protection by day 6. These data demonstrate the safety, immunogenicity, and efficacy of novel insect-specific EILV-based chimeras as potential EEEV and VEEV vaccines.

Original languageEnglish (US)
Article numbere01274-17
JournalJournal of Virology
Volume92
Issue number4
DOIs
StatePublished - Feb 1 2018

Fingerprint

Alphavirus
lethal genes
Venezuelan Equine Encephalitis Viruses
Venezuelan equine encephalitis virus
Insects
Vaccines
chimerism
vaccines
Viruses
viruses
insects
dosage
Vertebrates
vertebrates
Culicidae
Eastern equine encephalitis virus
Cryoelectron Microscopy
brain
animals
Aedes albopictus

Keywords

  • Alphavirus
  • Eilat virus
  • Emerging infectious diseases
  • Vaccines

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Novel insect-specific Eilat virus-based chimeric vaccine candidates provide durable, mono- and multivalent, single-dose protection against lethal alphavirus challenge. / Erasmus, Jesse H.; Seymour, Robert; Kaelber, Jason T.; Kim, Dal Y.; Leal, Grace; Sherman, Michael; Frolov, Ilya; Chiu, Wah; Weaver, Scott; Nasar, Farooq.

In: Journal of Virology, Vol. 92, No. 4, e01274-17, 01.02.2018.

Research output: Contribution to journalArticle

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