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<p>Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes severe chronic arthritis in humans and constitutes an expanding global threat. We previously reported that a single unadjuvanted dose of ChAdOx1 Chik vaccine was safe and elicited cross-protective functional antibodies against four distinctive CHIKV lineages in a Phase 1 trial. Here, we show that the CHIKV structural polyprotein encoded by ChAdOx1 Chik can assemble into CHIKV virus-like particles (VLPs) in mammalian cells. Cryo-EM derived reconstruction confirms that these CHIKV VLPs closely resemble the structure of the native virion and LC-MS demonstrates authentic E1/E2 glycosylation. In C57BL/6 mice, unadjuvanted CHIKV VLPs conferred significant protection against viremia and CHIKV-induced foot swelling. A head-to-head comparison of three adjuvant-free platforms encoding structural antigens derived from ChAdOx1 Chik showed that viral-vectors and VLPs induced similar CHIKV-neutralising antibody titres, both surpassing immunisation with soluble E2. Together, these structural and immunogenicity data support a mechanistic rationale that VLP assembly mediated by the clinically relevant ChAdOx1 Chik vaccine contributes to its vaccine-induced protection demonstrated in pre-clinical and clinical studies.</p>

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Structural and immunogenic characterisation of ChAdOx1 Chik-derived Chikungunya VLPs supports a mechanistic rationale for vaccine-induced protection

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月30日

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  • Young Chan Kim,
  • Xiyong Song,
  • Yasunori Watanabe,
  • Raquel de Oliveira Souza,
  • Robert Stass,
  • Sthefany Pagliari,
  • Max Crispin,
  • Beate Mareike Kümmerer,
  • Carla Claser,
  • Thomas A. Bowden,
  • Juha T. Huiskonen,
  • Arturo Reyes-Sandoval

摘要

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes severe chronic arthritis in humans and constitutes an expanding global threat. We previously reported that a single unadjuvanted dose of ChAdOx1 Chik vaccine was safe and elicited cross-protective functional antibodies against four distinctive CHIKV lineages in a Phase 1 trial. Here, we show that the CHIKV structural polyprotein encoded by ChAdOx1 Chik can assemble into CHIKV virus-like particles (VLPs) in mammalian cells. Cryo-EM derived reconstruction confirms that these CHIKV VLPs closely resemble the structure of the native virion and LC-MS demonstrates authentic E1/E2 glycosylation. In C57BL/6 mice, unadjuvanted CHIKV VLPs conferred significant protection against viremia and CHIKV-induced foot swelling. A head-to-head comparison of three adjuvant-free platforms encoding structural antigens derived from ChAdOx1 Chik showed that viral-vectors and VLPs induced similar CHIKV-neutralising antibody titres, both surpassing immunisation with soluble E2. Together, these structural and immunogenicity data support a mechanistic rationale that VLP assembly mediated by the clinically relevant ChAdOx1 Chik vaccine contributes to its vaccine-induced protection demonstrated in pre-clinical and clinical studies.