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| Title | Coxsackie B1 virus-like particle that lacks VP4 protein demonstrates improved vaccine scalability, stability and immunogenicity. |
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| Journal, issue, pages | J Biomed Sci, Vol. 33, Issue 1, Year 2026 |
| Publish date | Mar 26, 2026 |
 Authors | Saana Soppela / Henna-Maarit Kyröläinen / Alesia Levanova / Magloire Pandoua Nekoua / Martín González-Rodríguez / Heini Lehto / Kiran L L Ahmad / Sergey Guryanov / Vesa P Hytönen / Olli H Laitinen / Ilkka S Junttila / Didier Hober / Sarah J Butcher / Minna M Hankaniemi /   |
| PubMed Abstract | BACKGROUND: Enteroviruses, including coxsackievirus B1 (CVB1), cause severe diseases such as myocarditis and meningitis, but vaccines are lacking for most enteroviruses. Conserved and immunodominant ...BACKGROUND: Enteroviruses, including coxsackievirus B1 (CVB1), cause severe diseases such as myocarditis and meningitis, but vaccines are lacking for most enteroviruses. Conserved and immunodominant epitopes, such as VP4 region and VP1 N-terminus may limit vaccine efficacy by inducing non-neutralizing antibody responses. Virus-like particles (VLPs) mimic native viruses without genetic material and can be engineered to exclude epitopes. To address these challenges, we developed a CVB1-VLP lacking VP4. METHODS: Sequence conservation of CVB VP4 protein and the VP1 N-terminal PALXA region was assessed, and BALB/c mice were sequentially immunized with different formalin inactivated CVB vaccines. VLPΔVP4 was produced using baculovirus-insect cell expression system, was purified, and characterized by SDS-PAGE, transmission electron microscopy, dynamic light scattering, cryogenic electron microscopy, three-dimensional image reconstruction and atomic modelling. VLPΔVP4 stability was monitored over five years at 8 °C. Comprehensive preclinical experiments were conducted in mice with VLPΔVP4, VLPΔpalxa and inactivated CVB1. Vaccine immunogenicity was evaluated by neutralization assay, ELISA, ELISpot, and in vitro infection assays. RESULTS: VP4- and PALXA-regions were conserved among CVB serotypes and sequential mouse vaccinations confirmed the induction of antibodies against these regions, that should be avoided in vaccination. VLPΔVP4 exhibited > 95% purity, expected morphology (~ 30 nm), exceptional stability at 8 °C for five years, and the atomic modelling to 2.7 Å resolution showed that the particles were entirely in expanded form. Excluding VP4 from VLP improved production yield 3.5-fold, enhancing scalability of production. Immunological assays demonstrated that VLPΔVP4 induced slightly Th2-skewed response, but including adjuvant system 04 (AS04) in the vaccine induced balanced humoral and cellular immune response in mice. Sera from all vaccine groups modulated CVB1 infection, but IFN-α induction was lowest in VLP groups, suggesting reduced risk for antibody dependent enhancement of infection. VLPΔVP4 elicited significantly higher IFN-γ responses compared to other vaccines, indicating robust cellular immune response. Antibody responses were comparable across adjuvanted groups, but inclusion of VP4 in the vaccine correlated with weaker systemic T-cell responses. CONCLUSIONS: VLPΔVP4 represents a promising next-generation CVB vaccine candidate with broad applicability against enteroviruses. Removal of VP4 may mitigate the risk for non-beneficial immune imprinting while enabling high purity, long-term stability, and improved manufacturing efficiency. |
 External links | J Biomed Sci / PubMed:41888844 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 2.7 Å |
| Structure data | EMDB-56033, PDB-9tkm: |
| Source |
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 Keywords | VIRUS LIKE PARTICLE / CVB1 / VLP / vaccine candidate / enterovirus |
coxsackievirus b1