Enemy of My Enemy: A Novel Insect-Specific Flavivirus Offers a Promising Platform for a Zika Virus Vaccine.

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

doi:10.3390/vaccines9101142

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.

Highlights

Licensee MDPI, Basel, Switzerland.Members of the genus Flavivirus have a near-global distribution and remain among the most important arthropod-borne viruses affecting human and animal health
The Aripo virus (ARPV)/Zika virus (ZIKV) chimeric virus (Figure 1a) was recovered by transfection of transcribed RNA from the cDNA clone in C6/36 cells and the initial rescue titer was estimated at 4.5 × 107 genome copies (GC)/mL
ARPV/ZIKV titers began to decline after 96 hpi whereas ARPV plateaued, but no significant differences were observed between groups

Summary

Introduction

Licensee MDPI, Basel, Switzerland.Members of the genus Flavivirus (family, Flaviviridae) have a near-global distribution and remain among the most important arthropod-borne viruses (arboviruses) affecting human and animal health. Since 2007, the Zika virus (ZIKV) emerged as a serious public health threat in Southeast Asia, the South Pacific and South and Central America [1]. Associated with Guillain-Barré syndrome (a serious and sometimes fatal paralytic disease of the peripheral nervous system [2]) and congenital Zika syndrome (CZS), which includes microcephaly—a major neonatal malformation that is 20 times more likely to occur postZIKV infection of pregnant mothers [3]. In 2016 alone, an estimated 29% of babies born to ZIKV-infected mothers in some regions of Brazil exhibited developmental abnormalities [5,6]. The threat of ZIKV is further exacerbated by its capacity to be transmitted via alternative routes, such as sexual and perinatal, and, possibly, via blood-transfusion [7]

Methods

Results

Conclusion