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Immunological and transcriptomic profile of chimeric live-attenuated Zika vaccine linked to protection in non-human primates #MMPMID41390746
Ma J; Malengier-Devlies B; Verstrepen BE; Alpizar YA; Vercruysse T; Javarappa MPA; Sanchez-Felipe L; Koopman G; de Groot NG; Matthys P; Neyts J; Verschoor EJ; Coelmont L; Thibaut HJ; Van Weyenbergh J; Dallmeier K
Nat Commun 2025[Dec]; ? (?): ? PMID41390746show ga
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.
Nat+Commun 2025 ; ? (?): ?
