ENVELOPED VIRUS-LIKE PARTICLES (eVLPs) EXPRESSING MODIFIED FORMS OF ZIKA VIRUS PROTEINS E AND NS1 PROTECT MICE FROM ZIKA VIRUS INFECTION

作者: Anne-Catherine Fluckiger , Jasminka Bozic , Abebaw Diress , Barthelemy Ontsouka , Tanvir Ahmed

DOI: 10.1101/666966

关键词: Zika virusImmunityVirologyNeutralizing antibodyBiologyAntibodyMurine leukemia virusImmunogenicityTiterVaccination

摘要: Abstract While Zika virus (ZIKV) infection induces mild disease in the majority of cases, it has been identified as responsible for microcephaly and severe neurological disorders recent 2015-2016 outbreaks South America Caribbean. Since then, several prophylactic vaccine strategies have studied. Here, we describe development a ZIKV candidate consisting bivalent enveloped virus-like particles (eVLPs) expressing modified form E truncated NS1 (EG/NS1) proteins. In EG/NS1, transmembrane/cytoplasmic tail replaced with those domains from VSV G protein β-domain was fused in-frame to Gag Moloney murine leukemia (MLV). Immunization BALB/C mice demonstrated that EG/NS1 monovalent EG eVLPs induced comparable levels antibody (Ab) titers but much higher neutralizing activity, naturally acquired anti-ZIKV immunity. contrast, did not induce significant anti-NS1 Ab response promoted strong T cell immunity also elicited eVLPs. challenge studies C57BL/6-IFNαR−/− conferred 100% protection against clinical after compared 80% eVLP vaccination, correlating overt signs infection. Author Summary caused rapidly spreading epidemics potentially symptoms including new born babies. Rapid progress made vaccines under evaluation no or treatment is yet available. this context, produced tested recombinant incorporate one two proteins, optimal efficacy. Our immunogenicity showed synergistic effect both proteins vaccine. enhancing production by protein. experiments, protected These products could be further used explore correlates evaluated candidates.

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