A chimeric dengue virus vaccine candidate delivered by high density microarray patches protects against infection in mice

Jovin J Y Choo,Daniel Watterson,David A Muller,Paul R Young,Jody Hobson-Peters,Connor A P Scott,Laura J Vet,Alexandra C I Depelsenaire,Jessica J Harrison,Roy A Hall,Germain J P Fernando,Christopher L D Mcmillan

doi:10.1038/s41541-021-00328-1

Jovin J Y Choo, Daniel Watterson + Show 10 more

Open Access

https://doi.org/10.1038/s41541-021-00328-1

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Abstract

Dengue viruses (DENV) cause an estimated 390 million infections globally. With no dengue-specific therapeutic treatment currently available, vaccination is the most promising strategy for its control. A wide range of DENV vaccines are in development, with one having already been licensed, albeit with limited distribution. We investigated the immunogenicity and protective efficacy of a chimeric virus vaccine candidate based on the insect-specific flavivirus, Binjari virus (BinJV), displaying the structural prM/E proteins of DENV (BinJ/DENV2-prME). In this study, we immunized AG129 mice with BinJ/DENV2-prME via a needle-free, high-density microarray patch (HD-MAP) delivery system. Immunization with a single, 1 µg dose of BinJ/DENV2-prME delivered via the HD-MAPs resulted in enhanced kinetics of neutralizing antibody induction when compared to needle delivery and complete protection against mortality upon virus challenge in the AG129 DENV mouse model.

Highlights

Dengue is the most significant mosquito-borne viral disease throughout the world’s tropical zone[1,2]
We have recently reported the development of a new chimeric virus system to produce flaviviral vaccine candidates using a newly discovered insect-specific flavivirus (ISF) named Binjari virus (BinJV)[12]
We further showed that vaccinated mice induced potent neutralizing antibodies against Dengue viruses (DENV), and that by combining the BinJ/DENV2prME antigen with the high-density microarray patch (HD-MAP) vaccine delivery platform, complete protection from virus challenge of AG129 mice could be elicited using a single unadjuvanted dose of 1 μg of BinJ/

Summary

Introduction

Dengue is the most significant mosquito-borne viral disease throughout the world’s tropical zone[1,2]. Patients infected with DENV can experience a range of clinical outcomes, depending on their age and immunocompetency For those that develop symptoms, the clinical spectrum ranges from dengue fever, a self-limiting illness, to severe dengue haemorrhagic fever or potentially fatal dengue shock syndrome[4,5,6]. Cross-protection to heterologous serotypes following primary infection is limited, after which the risk of severe dengue disease increases when infected by a second virus serotype[3]. This increased susceptibility to severe disease following secondary infection with a heterologous virus serotype is explained by the phenomenon known as antibodydependent enhancement[7,8]. It is postulated that the induction of cross-reactive antibodies bind to the secondary virus, facilitating virus entry through Fc-mediated endocytosis, resulting in increased viral replication and a dysregulated immune response leading to vascular leak and severe disease[9]

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