Multivalent DNA Vaccines as A Strategy to Combat Multiple Concurrent Epidemics: Mosquito-Borne and Hemorrhagic Fever Viruses.

Jingjing Jiang,Connie S Schmaljohn,Preeti Bangalore,Holly Pugh,Ami Patel,David B Weiner,Jian Yan,Katherine Schultheis,Kathleen A Cashman,Dustin Elwood,Kate E Broderick,Jared Tur,Sagar B Kudchodkar,Stephanie J Ramos,Laurent M Humeau,Kar Muthumani,Jewell Walters

doi:10.3390/v13030382

Abstract

The emergence of multiple concurrent infectious diseases localized in the world creates a complex burden on global public health systems. Outbreaks of Ebola, Lassa, and Marburg viruses in overlapping regions of central and West Africa and the co-circulation of Zika, Dengue, and Chikungunya viruses in areas with A. aegypti mosquitos highlight the need for a rapidly deployable, safe, and versatile vaccine platform readily available to respond. The DNA vaccine platform stands out as such an application. Here, we present proof-of-concept studies from mice, guinea pigs, and non-human primates for two multivalent DNA vaccines delivered using in vivo electroporation (EP) targeting mosquito-borne (MMBV) and hemorrhagic fever (MHFV) viruses. Immunization with MMBV or MHFV vaccines via intradermal EP delivery generated robust cellular and humoral immune responses against all target viral antigens in all species. MMBV vaccine generated antigen-specific binding antibodies and IFNγ-secreting lymphocytes detected in NHPs up to six months post final immunization, suggesting induction of long-term immune memory. Serum from MHFV vaccinated NHPs demonstrated neutralizing activity in Ebola, Lassa, and Marburg pseudovirus assays indicating the potential to offer protection. Together, these data strongly support and demonstrate the versatility of DNA vaccines as a multivalent vaccine development platform for emerging infectious diseases.

Highlights

Based on the success of other ID-EP administered DNA vaccines and adding to our multivalent DNA vaccine capabilities, we sought to investigate the possibility of ID-EP codelivery of pEBOV, pMARV, and pLASV DNA vaccines as a multivalent hemorrhagic fever virus (MHFV) vaccine in Guinea pigs, a suitable small animal model of intradermal vaccine delivery [17]
There were overlapping areas of EBOV, MARV, and LASV GP expression in treated skin, indicating co-transfection of tissue at the delivery site (Figure 1D). This data confirms successful delivery and expression of the MHFV DNA vaccine, but this level of visualization serves as a proof of concept for co-expression of multivalent DNA vaccines in the skin following intradermal delivery with
One example mentioned earlier is the increase in reports about concurrent outbreaks of ZIKV, DENV, and CHIKV in A. aegypti mosquito prone areas

Summary

Introduction

Emerging infectious disease outbreaks have significantly increased in the past decades largely due to climate and environmental change, increased international travel and trade, and rapid population growth. Studies have shown that more than half of emerging infectious diseases originate from wildlife in areas with socio-economic disadvantages and limited infrastructure to control these outbreaks [1]. Concurrent outbreaks of multiple emerging infectious diseases further complicate the problem of containment in lower income regions. Multiple hemorrhagic fever viruses have been reported to occur in overlapping regions of Africa. The recent 2013–2016 Ebola virus (EBOV) outbreak

Methods

Results

Conclusion