Immunological and transcriptomic profile of chimeric live-attenuated Zika vaccine linked to protection in non-human primates
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.
Authors
- Ernst J. Verschoor (ORCID: https://orcid.org/0000-0003-0912-2074)
- Mahadesh Prasad Arkalagud Javarappa (ORCID: https://orcid.org/0000-0002-5792-6600)
- Lotte Coelmont (ORCID: https://orcid.org/0000-0002-7888-4534)
- Johan Van Weyenbergh (ORCID: https://orcid.org/0000-0003-3234-8426)
- Yeranddy A. Alpízar (ORCID: https://orcid.org/0000-0003-1959-5393)
- Gerrit Koopman (ORCID: https://orcid.org/0000-0002-3428-5978)
- Ji Ma (ORCID: https://orcid.org/0000-0002-0912-2632)
- Lorena Sánchez-Felipe (ORCID: https://orcid.org/0000-0002-6928-0931)
- Natasja G. de Groot (ORCID: https://orcid.org/0000-0001-6699-9345)
- Thomas Vercruysse (ORCID: https://orcid.org/0000-0002-8649-777X)
- Bert Malengier‐Devlies (ORCID: https://orcid.org/0000-0003-3527-1145)
- Hendrik Jan Thibaut (ORCID: https://orcid.org/0000-0001-5785-8276)
- Babs E. Verstrepen (ORCID: https://orcid.org/0000-0002-4666-0798)
- Patrick Matthys (ORCID: https://orcid.org/0000-0002-9685-6836)
- Kai Dallmeier (ORCID: https://orcid.org/0000-0002-8117-9166)
- Johan Neyts (ORCID: https://orcid.org/0000-0002-0033-7514)
Institutions
- Rega Institute for Medical Research (BE)
- Erasmus MC (NL)
- Biomedical Primate Research Centre (NL)
- MRC Centre for Regenerative Medicine (GB)
- Queen Astrid Military Hospital (BE)
- Institut de Recherche Vaccinale (FR)
- University of Edinburgh (GB)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-12-13
- DOI
- https://doi.org/10.1038/s41467-025-66073-4
- Primary Topic
- Mosquito-borne diseases and control
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- European Commission
- Fonds Wetenschappelijk Onderzoek
- Università degli Studi di Padova
- KU Leuven
- Vlaamse regering