Document Type
Article
Author ORCID Identifier
Jeffrey B. Mason https://orcid.org/0000-0003-2459-1186
Irina A. Polejaeva https://orcid.org/0000-0002-0858-5889
Kenneth L. White https://orcid.org/0000-0003-0368-886X
Xin Dai https://orcid.org/0000-0001-8821-0042
Young-Min Lee https://orcid.org/0000-0002-3974-3405
Journal/Book Title/Conference
International Journal of Molecular Sciences
Volume
26
Issue
1
Publisher
MDPI AG
Publication Date
12-29-2024
Journal Article Version
Version of Record
First Page
1
Last Page
29
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Abstract
Zika virus (ZIKV) is a medically important mosquito-borne orthoflavivirus, but no vaccines are currently available to prevent ZIKV-associated disease. In this study, we compared three recombinant chimeric viruses developed as candidate vaccine prototypes (rJEV/ZIKVMR-766, rJEV/ZIKVP6-740, and rJEV/ZIKVPRVABC-59), in which the two neutralizing antibody-inducing prM and E genes from each of three genetically distinct ZIKV strains were used to replace the corresponding genes of the clinically proven live-attenuated Japanese encephalitis virus vaccine SA14-14-2 (rJEV). In WHO-certified Vero cells (a cell line suitable for vaccine production), rJEV/ZIKVP6-740 exhibited the slowest viral growth, formed the smallest plaques, and displayed a unique protein expression profile with the highest ratio of prM to cleaved M when compared to the other two chimeric viruses, rJEV/ZIKVMR-766 and rJEV/ZIKVPRVABC-59, as well as their vector, rJEV. In IFNAR−/− mice, an animal model of ZIKV infection, subcutaneous inoculation of rJEV/ZIKVP6-740 caused a low-level localized infection limited to the spleen, with no clinical signs of infection, weight loss, or mortality; in contrast, the other two chimeric viruses and their vector caused high-level systemic infections involving multiple organs, consistently leading to clear clinical signs of infection, rapid weight loss, and 100% mortality. Subsequently, subcutaneous immunization with rJEV/ZIKVP6-740 proved highly effective, offering complete protection against a lethal intramuscular ZIKV challenge 28 days after a single-dose immunization. This protection was specific to ZIKV prM/E and likely mediated by neutralizing antibodies targeting ZIKV prM/E. Therefore, our data indicate that the chimeric virus rJEV/ZIKVP6-740 is a highly promising vaccine prototype for developing a safe and effective vaccine for inducing neutralizing antibody-mediated protective immunity against ZIKV.
Recommended Citation
Song, B.-H.; Frank, J.C.; Yun, S.-I.; Julander, J.G.; Mason, J.B.; Polejaeva, I.A.; Davies, C.J.; White, K.L.; Dai, X.; Lee, Y.-M. Comparison of Three Chimeric Zika Vaccine Prototypes Developed on the Genetic Background of the Clinically Proven Live-Attenuated Japanese Encephalitis Vaccine SA14-14-2. Int. J. Mol. Sci. 2025, 26, 195. https://doi.org/10.3390/ijms26010195