Abstract
Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that has spread to more than 70 countries worldwide since 2015. Despite active research, there are currently no licensed vaccines or therapeutics. We have previously reported the development of various adenoviral vectored vaccine candidates (ChAdOx1 ZIKV) with the ability to stimulate effective immunity in mice and provide protection upon a ZIKV challenge model, using a non-adjuvanted single vaccination approach. In this study, we constructed various modified vaccinia Ankara (MVA) viruses to express the ZIKV Envelope (E) with modifications on the precursor membrane (prM) or on the C-terminus envelope transmembrane domain (TM), similar to our ChAdOx1 vaccine candidates. MVA-ZIKV vaccine candidates were evaluated as a non-adjuvanted single vaccination regimen against a ZIKV Brazilian isolate, using viraemia as the correlate of protection. Here, we report the induction of a modest level of anti-ZIKV E antibodies by all MVA vectored vaccines and sub-optimal efficacy in a ZIKV challenge model. Our results indicate the requirement of additional strategies when using MVA-ZIKV vaccines to afford sterile protection upon a non-adjuvanted and single vaccination regime.
Highlights
Zika virus (ZIKV) is a mosquito-borne flavivirus virus that belongs to the family Flaviviridae [1].After its first discovery in 1947 from a sentinel rhesus monkey in Uganda, ZIKV caused sporadic outbreaks in Africa and South Asia until the occurrence of major outbreaks in Micronesia in 2007 and French Polynesia in 2013 [2,3]
This study reports that modified vaccinia Ankara (MVA) ZIKV vaccine candidates may be a limited candidate for further clinical assessment, if used as a single-vaccination approach
To generate MVA-based ZIKV vaccine candidates, we sub-cloned each of the ZIKV transgenes with parental MVA plasmid (Figure 1a)
Summary
Zika virus (ZIKV) is a mosquito-borne flavivirus virus that belongs to the family Flaviviridae [1].After its first discovery in 1947 from a sentinel rhesus monkey in Uganda, ZIKV caused sporadic outbreaks in Africa and South Asia until the occurrence of major outbreaks in Micronesia in 2007 and French Polynesia in 2013 [2,3]. Zika virus (ZIKV) is a mosquito-borne flavivirus virus that belongs to the family Flaviviridae [1]. ZIKV has spread rapidly throughout the Americas since its first report in Brazil in 2015 [4], affecting more than 70 countries worldwide [5]. ZIKV is classified into two lineages: African (AF) and Asian (AS) [6]. The Asian lineage is causing the current outbreaks occurring worldwide. The main vector for urban transmission of ZIKV is the Aedes mosquito, sexual contact and vertical transmission are responsible for the virus dissemination [7]. Infection by ZIKV is associated with neurological complications, such as microcephaly in foetuses and Guillain–Barré syndrome (GBS) in adults, considered congenital zika syndrome (CZS) [8,9,10].
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