Palur, V. R., Chen, F.-C., Wu, S.-R., Chen, G.-W., Bond, P. J., Chao, D.-Y., & Marzinek, J. K. (2025). An integrative approach to rational engineering of dengue virus-like particles. Cell Reports Physical Science, 6(9), 102814. https://doi.org/10.1016/j.xcrp.2025.102814
Abstract:
Virus-like particles (VLPs) are promising vaccine candidates due to their noninfectious and highly immunogenic
nature. Enveloped VLPs are unstable and heterogeneous in size because they lack a viral genomic
core, yet they can induce a robust immune response. This motivates the characterization of their biophysical
and structural properties to enable rational design of stable, highly immunogenic particles. We employed an
integrative approach combining multiscale modeling, structural analyses, and in vitro experiments to gain
molecular insights into the factors governing VLP stability, homogeneity, secretion, and antibody binding.
We focused on dengue virus VLPs, which elicit neutralizing antibodies similar to infectious virions. Systematic
introduction of mutations facing lipid tails in the stem helix of the chimeric E protein, guided by molecular
simulations, allowed modulation of secretion efficiency and immunogenicity. Overall, this work highlights the
role of envelope protein-lipid interactions in maintaining VLP stability and yield, guiding engineering of
improved VLP-based vaccines.
License type:
Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Funding Info:
This research / project is supported by the A*STAR - Advanced Manufacturing and Engineering Young Individual Research Grant
Grant Reference no. : A2084c0160
This research / project is supported by the National Research Foundation (NRF) - Competitive Research Programme (CRP)
Grant Reference no. : NRF-CRP27-2021-0003