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Basic Characteristics of Mutations
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Mutation Site
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D4W |
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Mutation Site Sentence
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Thus, vIND-ZIKV (D4W) was selected as the vaccine candidate to progress to further studies (referred to from now on as vIND-ZIKV). |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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E |
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Standardized Encoding Gene
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envelope
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Genotype/Subtype
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Asian |
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Viral Reference
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KU497555.1
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Functional Impact and Mechanisms
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Disease
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Cell line
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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- |
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Location
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Asia |
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Literature Information
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PMID
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33753816
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Title
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Single dose of a replication-defective vaccinia virus expressing Zika virus-like particles is protective in mice
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Author
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Jasperse B,O'Connell CM,Wang Y,Verardi PH
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Journal
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Scientific reports
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Journal Info
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2021 Mar 22;11(1):6492
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Abstract
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Zika virus (ZIKV), a flavivirus transmitted primarily by infected mosquitos, can cause neurological symptoms such as Guillian-Barre syndrome and microcephaly. We developed several vaccinia virus (VACV) vaccine candidates for ZIKV based on replication-inducible VACVs (vINDs) expressing ZIKV pre-membrane (prM) and envelope (E) proteins (vIND-ZIKVs). These vIND-ZIKVs contain elements of the tetracycline operon and replicate only in the presence of tetracyclines. The pool of vaccine candidates was narrowed to one vIND-ZIKV containing a novel mutation in the signal peptide of prM that led to higher expression and secretion of E and production of virus-like particles, which was then tested for safety, immunogenicity, and efficacy in mice. vIND-ZIKV grows to high titers in vitro in the presence of doxycycline (DOX) but is replication-defective in vivo in the absence of DOX, causing no weight loss in mice. C57BL/6 mice vaccinated once with vIND-ZIKV in the absence of DOX (as a replication-defective virus) developed robust levels of E-peptide-specific IFN-gamma-secreting splenocytes and anti-E IgG titers, with modest levels of serum-neutralizing antibodies. Vaccinated mice treated with anti-IFNAR1 antibody were completely protected from ZIKV viremia post-challenge after a single dose of vIND-ZIKV. Furthermore, mice with prior immunity to VACV developed moderate anti-E IgG titers that increased after booster vaccination, and were protected from viremia only after two vaccinations with vIND-ZIKV.
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Sequence Data
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-
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