Send to

Choose Destination
NPJ Vaccines. 2018 Dec 13;3:56. doi: 10.1038/s41541-018-0092-2. eCollection 2018.

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

Author information

KU Leuven Department of Microbiology and Immunology, Rega Institute, Laboratory of Virology and Chemotherapy, Leuven, Belgium.
2GIGA-Neurosciences, Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège, C.H.U. Sart Tilman, Liège, Belgium.
3Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, Sao Paulo, Brazil.
Contributed equally


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 × 102 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 (105 LD50) 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.

Conflict of interest statement

D.B.K., N.M., M.A.S., J.N., and K.D. have filed a patent application claiming the discovery and use of chimeric yellow fever—Zika virus vaccines. The remaining authors declare no competing interests.

Supplemental Content

Full text links

Icon for PubMed Central
Loading ...
Support Center