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Virus-like Particles (VLPs) are non-infectious nanoparticles formed by viral structural proteins that retain the geometric structure and immunogenicity of native viruses without genetic material. Among various VLP sources, RNA bacteriophages offer distinct advantages over eukaryotic viral VLPs, including lower production costs, simplified large-scale manufacturing, and absence of pre-existing host antibodies. Their high-density multivalent antigen display effectively promotes B-cell receptor crosslinking and enhances immune responses.
Figure 1. Bacteriophage VLP assembly and workflow overview
Creative Biogene provides comprehensive solutions from antigen design to vaccine development using RNA bacteriophage VLP technology platforms, enabling rapid development and commercialization of next-generation vaccines.
We work with several well-established bacteriophage platforms, each offering unique advantages for different applications.
| Phage Type | Host | Capsid Structure | Modification Sites | Key Advantages |
| MS2 | E. coli | Icosahedral, 180 subunits | AB loop, N-terminus | SCD enhancement, HPV L2 display, high-copy presentation |
| Qβ | E. coli | Similar to MS2, readthrough protein | C-terminus, thiol coupling | PCSK9 peptide conjugation, >360 copies via SMPH |
| AP205 | E. coli | Circular permutation, β-sheet core | N/C termini | SpyTag system, thermostable, large protein compatibility |
| PP7 | E. coli | MS2-like with SCD design | Dimer interface | Zika epitope insertion, high flexibility |
| P22 | Salmonella | Capsid + scaffolding proteins (~58 nm) | Internal/surface display | Enzyme encapsulation, B/T epitope co-display |
Our antigen display technologies are designed to match your specific requirements rather than forcing your project into a predetermined approach.
Genetic Insertion
Foreign sequences are inserted into AB loops or N/C termini of capsid proteins via molecular cloning. Structural modeling guides site selection to ensure proper folding and assembly. Single-Chain Dimer (SCD) design extends insert length capacity, supporting larger epitope display.
Chemical Conjugation
Bifunctional crosslinkers (e.g., SMPH, EDC/NHS) covalently attach antigens, including glycopeptides and small molecules, to VLP surfaces. Each particle can present 240–360 antigen copies. Services include crosslinker selection, reaction optimization, and purification.
Bioconjugation
Bioorthogonal systems like SpyTag/SpyCatcher form covalent isopeptide bonds for stable antigen attachment, preserving native structure and activity. Services cover tag design, VLP vector construction, and reaction tuning for high-efficiency conjugation.
With a focus on technical precision and reliability, we offer integrated VLP development services that span from antigen design to production scale-up.
To address common challenges in VLP development, we offer targeted solutions:
To ensure consistency across all phases:
| Service Type | Typical Timeline |
| Platform evaluation | 2-3 weeks |
| VLP construction | 4-6 weeks |
| Production & purification | 3-4 weeks |
| Basic characterization | 1-2 weeks |
| Immunogenicity testing | 6-8 weeks |
Timelines may vary based on project complexity and specific requirements.
We believe in building partnerships with our clients. Whether you're developing your first VLP vaccine or looking to optimize existing platforms, our team is here to support your goals.
Contact us to discuss:
Creative Biogene specializes in custom biotechnology solutions. Our RNA bacteriophage VLP services represent one of our focused capabilities, designed to support vaccine and therapeutic development in both academic and commercial settings.
Q: How can the immunogenicity and protective efficacy of bacteriophage VLPs be evaluated?
A: To assess the immunogenicity and protective efficacy of bacteriophage VLPs, animals are immunized with 5–50 µg of VLPs, with or without adjuvants, followed by booster doses at 2–4 week intervals. Antibody responses are measured by ELISA, and neutralization is evaluated using pseudovirus assays. Cellular immunity is assessed via ELISpot for IFN-γ and flow cytometry for CD8⁺ T cells. In vivo challenge or tumor models are used to confirm protection by measuring viral load or tumor suppression.
Q: What strategies are used to control endotoxin levels during VLP production?
A: Endotoxin is reduced by using low-endotoxin bacterial strains and applying purification steps like detergent phase separation and multi-step chromatography. Endotoxin levels are measured by LAL assay, and biocompatibility is confirmed through in vitro immune cell tests.
Q: How can assembly failure caused by long peptide insertions be resolved?
A: When long peptide sequences interfere with proper VLP assembly, several strategies can be used to restore structural integrity, including redesigning the protein construct for better stability, using flexible linkers to reduce steric clashes, and optimizing expression conditions such as lowering temperature or co-expressing chaperone proteins to aid proper folding. Alternatively, if direct genetic insertion fails, the peptides can be attached to pre-formed VLPs through post-expression coupling or modular assembly techniques, allowing for effective antigen display without disrupting particle formation.
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