Structural and immunogenic characterisation of ChAdOx1 Chik-derived Chikungunya VLPs supports a mechanistic rationale for vaccine-induced protection
7 affiliations
- 1Department of Paediatrics, Oxford Vaccine Group, University of Oxford
- 2Institute of Biotechnology, Helsinki Institute of Life Science HiLIFE, University of Helsinki
- 3Division of Structural Biology, Centre for Human Genetics, University of Oxford
- 4Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo
- 5School of Biological Sciences, University of Southampton
- 6Institute of Virology, Medical Faculty, University of Bonn
- 7Instituto Politécnico Nacional (IPN). Unidad Adolfo López Mateos
Abstract
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.
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BibTeX
@article{kim2026structural,
title = {{Structural and immunogenic characterisation of ChAdOx1 Chik-derived Chikungunya VLPs supports a mechanistic rationale for vaccine-induced protection}},
author = {Young Chan Kim and Xiyong Song and Yasunori Watanabe and Raquel de Oliveira Souza and Robert Stass and Sthefany Pagliari and Max Crispin and Beate Mareike Kümmerer and Carla Claser and Thomas A. Bowden and Juha T. Huiskonen and Arturo Reyes-Sandoval},
journal = {npj Viruses},
year = {2026},
month = jun,
doi = {10.1038/s44298-026-00207-3},
url = {https://doi.org/10.1038/s44298-026-00207-3},
note = {CC BY},
}
RIS
TY - JOUR
TI - Structural and immunogenic characterisation of ChAdOx1 Chik-derived Chikungunya VLPs supports a mechanistic rationale for vaccine-induced protection
AU - Young Chan Kim
AU - Xiyong Song
AU - Yasunori Watanabe
AU - Raquel de Oliveira Souza
AU - Robert Stass
AU - Sthefany Pagliari
AU - Max Crispin
AU - Beate Mareike Kümmerer
AU - Carla Claser
AU - Thomas A. Bowden
AU - Juha T. Huiskonen
AU - Arturo Reyes-Sandoval
PY - 2026
DA - 2026/06/01
JO - npj Viruses
DO - 10.1038/s44298-026-00207-3
UR - https://doi.org/10.1038/s44298-026-00207-3
AB - 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.
SN - 2948-1767
ER -