{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kum DB"],"funding":["EC | Horizon 2020"],"pagination":["56"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6292895"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["3"],"pubmed_abstract":["The recent Zika virus (ZIKV) epidemic in the Americas led to an intense search for therapeutics and vaccines. Here we report the engineering of a chimeric virus vaccine candidate (YF-ZIKprM/E) by replacing the antigenic surface glycoproteins and the capsid anchor of YFV-17D with those of a prototypic Asian lineage ZIKV isolate. By intracellular passaging, a variant with adaptive mutations in the E protein was obtained. Unlike YFV-17D, YF-ZIKprM/E replicates poorly in mosquito cells. Also, YF-ZIKprM/E does not cause disease nor mortality in interferon α/β, and γ receptor KO AG129 mice nor following intracranial inoculation of BALB/c pups. A single dose as low as 1 × 10<sup>2</sup> PFU results, as early as 7 days post vaccination, in seroconversion to neutralizing antibodies and confers full protection in AG129 mice against stringent challenge with a lethal inoculum (10<sup>5</sup> LD<sub>50</sub>) of either homologous or heterologous ZIKV strains. Induction of multi-functional CD4<sup>+</sup> and CD8<sup>+</sup> T cell responses against ZIKV structural and YFV-17D non-structural proteins indicates that cellular immunity may also contribute to protection. Vaccine immunogenicity and protection was confirmed in other mouse strains, including after temporal blockade of interferon-receptors in wild-type mice to facilitate ZIKV replication. Vaccination of wild-type NMRI dams with YF-ZIKprM/E results in complete protection of foetuses against brain infections and malformations following a stringent intraplacental challenge with an epidemic ZIKV strain. The particular characteristic of YF-ZIKprM/E in terms of efficacy and its marked attenuation in mice warrants further exploration as a vaccine candidate."],"journal":["NPJ vaccines"],"pubmed_title":["A yellow fever-Zika chimeric virus vaccine candidate protects against Zika infection and congenital malformations in mice."],"pmcid":["PMC6292895"],"funding_grant_id":["734548","733176","734584"],"pubmed_authors":["Kum DB","Dallmeier K","Schmid MA","Kaptein S","Gladwyn-Ng I","Alfano C","Nguyen L","Boudewijns R","Schols D","Neyts J","Marques RE","Mishra N","Ma J"],"additional_accession":[]},"is_claimable":false,"name":"A yellow fever-Zika chimeric virus vaccine candidate protects against Zika infection and congenital malformations in mice.","description":"The recent Zika virus (ZIKV) epidemic in the Americas led to an intense search for therapeutics and vaccines. Here we report the engineering of a chimeric virus vaccine candidate (YF-ZIKprM/E) by replacing the antigenic surface glycoproteins and the capsid anchor of YFV-17D with those of a prototypic Asian lineage ZIKV isolate. By intracellular passaging, a variant with adaptive mutations in the E protein was obtained. Unlike YFV-17D, YF-ZIKprM/E replicates poorly in mosquito cells. Also, YF-ZIKprM/E does not cause disease nor mortality in interferon α/β, and γ receptor KO AG129 mice nor following intracranial inoculation of BALB/c pups. A single dose as low as 1 × 10<sup>2</sup> PFU results, as early as 7 days post vaccination, in seroconversion to neutralizing antibodies and confers full protection in AG129 mice against stringent challenge with a lethal inoculum (10<sup>5</sup> LD<sub>50</sub>) of either homologous or heterologous ZIKV strains. Induction of multi-functional CD4<sup>+</sup> and CD8<sup>+</sup> T cell responses against ZIKV structural and YFV-17D non-structural proteins indicates that cellular immunity may also contribute to protection. Vaccine immunogenicity and protection was confirmed in other mouse strains, including after temporal blockade of interferon-receptors in wild-type mice to facilitate ZIKV replication. Vaccination of wild-type NMRI dams with YF-ZIKprM/E results in complete protection of foetuses against brain infections and malformations following a stringent intraplacental challenge with an epidemic ZIKV strain. The particular characteristic of YF-ZIKprM/E in terms of efficacy and its marked attenuation in mice warrants further exploration as a vaccine candidate.","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018","modification":"2026-05-06T03:30:34.511Z","creation":"2019-03-27T00:13:14Z"},"accession":"S-EPMC6292895","cross_references":{"pubmed":["30564463"],"doi":["10.1038/s41541-018-0092-2"]}}