Enemy of my enemy: A novel insect-specific flavivirus offers a promising platform for a zika virus vaccine

Danielle L. Porier, Sarah N. Wilson, Dawn I. Auguste, Andrew Leber, Sheryl Coutermarsh-Ott, Irving C. Allen, Clayton C. Caswell, James A. Budnick, Josep Bassaganya-Riera, Raquel Hontecillas, James Weger-Lucarelli, Scott C. Weaver, Albert Auguste

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Vaccination remains critical for viral disease outbreak prevention and control, but conventional vaccine development typically involves trade-offs between safety and immunogenicity. We used a recently discovered insect-specific flavivirus as a vector in order to develop an exceptionally safe, flavivirus vaccine candidate with single-dose efficacy. To evaluate the safety and efficacy of this platform, we created a chimeric Zika virus (ZIKV) vaccine candidate, designated Aripo/Zika virus (ARPV/ZIKV). ZIKV has caused immense economic and public health impacts throughout the Americas and remains a significant public health threat. ARPV/ZIKV vaccination showed exceptional safety due to ARPV/ZIKV’s inherent vertebrate host-restriction. ARPV/ZIKV showed no evidence of replication or translation in vitro and showed no hematological, histological or pathogenic effects in vivo. A single-dose immunization with ARPV/ZIKV induced rapid and robust neutralizing antibody and cellular responses, which offered complete protection against ZIKV-induced morbidity, mortality and in utero transmission in immune-competent and-compromised murine models. Splenocytes derived from vaccinated mice demonstrated significant CD4+ and CD8+ responses and significant cytokine production post-antigen exposure. Altogether, our results further support that chimeric insect-specific flaviviruses are a promising strategy to restrict flavivirus emergence via vaccine development.

Original languageEnglish (US)
Article number1142
JournalVaccines
Volume9
Issue number10
DOIs
StatePublished - Oct 2021

Keywords

  • Correlates of protection
  • Flavivirus
  • Insect-specific virus
  • Vaccine
  • Zika virus

ASJC Scopus subject areas

  • Immunology
  • Pharmacology
  • Drug Discovery
  • Infectious Diseases
  • Pharmacology (medical)

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