Authors: Ji Ma, Bert Malengier-Devlies, Babs E. Verstrepen, Yeranddy A. Alpizar, Thomas Vercruysse, Mahadesh Prasad Arkalagud Javarappa, Lorena Sanchez-Felipe, Gerrit Koopman, Natasja G. de Groot, Patrick Matthys, Johan Neyts, Ernst J. Verschoor, Lotte Coelmont, Hendrik Jan Thibaut, Johan Van Weyenbergh & Kai Dallmeier
Journal: Nature Communications
Published: 13 December 2025
DOI: https://doi.org/10.1038/s41467-025-66073-4
Immunological and transcriptomic profile of chimeric live-attenuated Zika vaccine linked to protection in non-human primates
Abstract
Zika virus (ZIKV) is typically mild in humans but can cause severe congenital defects when contracted during pregnancy. Chimeric live-attenuated vaccine candidate YF-ZIK previously showed protective efficacy against lethal infection and developmental abnormalities in mice after a single dose.
Here we demonstrate that YF-ZIK is safe, induces antiviral immunity, and protects rhesus macaques against high-dose experimental challenge. A single subcutaneous dose elicits neutralizing antibodies within 7–14 days, boosted by a second dose at 4 weeks. Passive serum transfer protects AG129 mice, supporting antibodies as a correlate of protection.
YF-ZIK triggers balanced Th1/Th2 responses and a transcriptional profile resembling the licensed YF17D vaccine, involving multiple pathways favoring polyvalent immunity. Upon challenge, vaccinated macaques show no detectable viral RNA nor seroconversion to anti-ZIKV NS1 antibodies, suggesting sterilizing immunity. Systems analysis identifies TNFRSF17 as predictor of antibody responses to YF-ZIK, and GNAS and CD207 (Langerin) as potentially linked to clinical outcomes.
The favorable preclinical safety, immunogenicity, and efficacy of YF-ZIK justify its future evaluation in humans.
Read the full article here: https://doi.org/10.1038/s41467-025-66073-4
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