Article (Périodiques scientifiques)
A yellow fever–Zika chimeric virus vaccine candidate protects against Zika infection and congenital malformations in mice
Kum, D. B.; Mishra, N.; Boudewijns, R. et al.
2018In npj Vaccines, 3 (1)
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Mots-clés :
Zika virus vaccine; Article; CD4+ T lymphocyte; CD8+ T lymphocyte; NMRI mouse; Zika fever; Zika virus
Résumé :
[en] 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 2 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 5 LD 50 ) of either homologous or heterologous ZIKV strains. Induction of multi-functional CD4 + and CD8 + 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. © 2018, The Author(s).
Disciplines :
Microbiologie
Auteur, co-auteur :
Kum, D. B.;  KU Leuven Department of Microbiology and Immunology, Rega Institute, Laboratory of Virology and Chemotherapy, Leuven, Belgium
Mishra, N.;  KU Leuven Department of Microbiology and Immunology, Rega Institute, Laboratory of Virology and Chemotherapy, Leuven, Belgium
Boudewijns, R.;  KU Leuven Department of Microbiology and Immunology, Rega Institute, Laboratory of Virology and Chemotherapy, Leuven, Belgium
Gladwyn-Ng, Ivan ;  GIGA-Neurosciences, Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège, C.H.U. Sart Tilman, Liège, Belgium
Alfano, Christian ;  Université de Liège - ULiège > Neurosciences-Molecular Regulation of Neurogenesis
Ma, J.;  KU Leuven Department of Microbiology and Immunology, Rega Institute, Laboratory of Virology and Chemotherapy, Leuven, Belgium
Schmid, M. A.;  KU Leuven Department of Microbiology and Immunology, Rega Institute, Laboratory of Virology and Chemotherapy, Leuven, Belgium
Marques, R. E.;  Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Sao Paulo, Brazil
Schols, D.;  KU Leuven Department of Microbiology and Immunology, Rega Institute, Laboratory of Virology and Chemotherapy, Leuven, Belgium
Kaptein, S.;  KU Leuven Department of Microbiology and Immunology, Rega Institute, Laboratory of Virology and Chemotherapy, Leuven, Belgium
Nguyen, Laurent  ;  Université de Liège - ULiège > Neurosciences-Molecular Regulation of Neurogenesis
Neyts, J.;  KU Leuven Department of Microbiology and Immunology, Rega Institute, Laboratory of Virology and Chemotherapy, Leuven, Belgium
Dallmeier, K.;  KU Leuven Department of Microbiology and Immunology, Rega Institute, Laboratory of Virology and Chemotherapy, Leuven, Belgium
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Langue du document :
Anglais
Titre :
A yellow fever–Zika chimeric virus vaccine candidate protects against Zika infection and congenital malformations in mice
Date de publication/diffusion :
2018
Titre du périodique :
npj Vaccines
eISSN :
2059-0105
Maison d'édition :
Nature
Volume/Tome :
3
Fascicule/Saison :
1
Peer reviewed :
Peer reviewed vérifié par ORBi
Disponible sur ORBi :
depuis le 16 janvier 2020

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