A yellow fever–Zika chimeric virus vaccine candidate protects against Zika infection and congenital malformations in mice

Kum, D. B.; Mishra, N.; Boudewijns, R.; Gladwyn-Ng, Ivan; Alfano, Christian; Ma, J.; Schmid, M. A.; Marques, R. E.; Schols, D.; Kaptein, S.; Nguyen, Laurent; Neyts, J.; Dallmeier, K.

doi:10.1038/s41541-018-0092-2

Article (Scientific journals)

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.

2018 • In npj Vaccines, 3 (1)

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https://hdl.handle.net/2268/243283

DOI
10.1038/s41541-018-0092-2

PubMed
30564463

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Keywords :

Zika virus vaccine; Article; CD4+ T lymphocyte; CD8+ T lymphocyte; NMRI mouse; Zika fever; Zika virus

Abstract :

[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 :

Microbiology

Author, co-author :

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

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Language :

English

Title :

A yellow fever–Zika chimeric virus vaccine candidate protects against Zika infection and congenital malformations in mice

Publication date :

2018

Journal title :

npj Vaccines

eISSN :

2059-0105

Publisher :

Nature Publishing Group

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Issue :

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since 16 January 2020

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