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<p>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 <i>TNFRSF17</i> as predictor of antibody responses to YF-ZIK, and <i>GNAS</i> and <i>CD207</i> (Langerin) as potentially linked to clinical outcomes. The favorable preclinical safety, immunogenicity, and efficacy of YF-ZIK justify its future evaluation in humans.</p>

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Immunological and transcriptomic profile of chimeric live-attenuated Zika vaccine linked to protection in non-human primates

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月13日

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  • 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

摘要

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.