Enveloped Virus-Like Particle Based Vaccines

Like parental viruses, virus-like particles can be either enveloped or non-enveloped and can be produced in different expression systems depending on their complexity. Enveloped virus-like particles (eVLPs) has the same size and structure as enveloped viruses and present antigens in their natural state for an improved immune response. With years of experience for VLP assemblies and advanced technologies, Creative Biolabs will help you develop novel, stable and efficient eVLP-based vaccine candidates. Count on us to help address your challenges and get your process going.

Enveloped Virus-Like Particles

Virus-like particles (VLPs) are non-infectious nanostructures composed of viral structural proteins morphologically resembling authentic virions. Based on the structure of viruses, VLPs can be divided into non-enveloped VLPs and enveloped VLPs (eVLPs). Several VLP-based vaccine candidates have been shown to be efficacious in preclinical and clinical trials. Some of them have reached the market and most are targeting non-enveloped viruses. Compared to non-enveloped VLPs, eVLPs are much more complex in composition. The presence of host cell-derived membranes provides additional possibilities for the integration of heterologous antigens and adjuvants. In addition, for different viral families, the origin and composition of the envelope vary, and usually depend on the assembly process of the virion in the natural host and the specific cell line used for production.

Fig.1 Enveloped Virus-Like Particles.

Assembly and Budding of eVLPs

In general, the self-assembly of eVLP involves two steps - the formation of internal structural proteins (core, capsid or matrix), and then membrane enclosure for further budding. Viral surface antigens, mainly glycoproteins, will be present in the envelope of eVLP and may enhance immunogenicity and serve as adjuvants. The correct folding of these viral antigens, especially glycosylation, plays an important role in the efficacy of eVLP-based vaccines because it is crucial for stability, immune recognition and pathogenicity. Like enveloped viruses, eVLPs obtain lipid membranes from host cells by budding. Depending on the virosome assembly process in the natural host, intracellular membrane compartments or some alternative pathway may be involved in the secretion of eVLP.

Our Expression Platforms for eVLPs

Bacteria is the most widely used expression system for manufacturing recombinant proteins. However, lacking of post- translational modification system and protein solubility problems make it not a proper platform for eVLP production. Creative Biolabs provides various expression platforms for our customers to choose from:

• Eukaryotic expression systems. Yeast expression systems have advantages such as scalable fermentation, low production costs, and post-translational modification system.
• Higher eukaryotic expression systems. Insect and mammalian cells have been extensively used for both intracellular and secretory production of eVLPs because of their more complex post-translational modification system and supporting most aspects of the virus life cycle.
• Baculovirus-insect cell expression system. As the most commonly used system for producing eVLPs, insect cell lines do not require CO₂, making scale up of protein production feasible. Stably transformed insect cells have become excellent tools for the production of secreted glycoproteins.
• Mammalian cell expression systems. The main advantage of mammalian cells is to perform complete post-translational modification of recombinant proteins. Several mammalian cell types, such as HEK293, CHO, and BHK-21 cell lines are extensively utilized for eVLP production.
• Plant expression systems. A plant can produce large quantities of recombinant protein at low cost, provide complex but distinctive post-translational modification, and bring a low-risk of introducing adventitious human pathogens.

Optimization Services

Technical challenges still remain in the production of eVLP-based vaccines. Creative Biolabs offers a series of optimization strategies to help you solve problems regarding the design, purification, and storage of eVLP based vaccines.

• Stability. eVLPs are more sensitive to the external environment (temperature, shear force, and chemical treatment) than the protein-only VLPs. This structural destruction further leads to the reduction in immunogenicity of eVLPs. Creative Biolabs provides chemical modification services for eVLPs to improve the particle thermostability.
• Expression level. Generally, the secretory expression of glycoproteins is difficult. Since budding from cell membrane to get envelop is a key step during the eVLP formation process, if eVLP is not efficiently secreted, a cell lysis or other extraction step might be required, and these steps increase the difficulty for further purification. Creative Biolabs provides a range of optimization services to improve the secretion potential for eVLP.
• Purification. Numerous impurities co-purified with eVLPs pose a daunting challenge. Diverse of purification methods have been developed in Creative Biolabs such as centrifugation, precipitation, ultrafiltration and chromatography.

Due to their simplicity, safety and favorable immunological characteristics to induce both humoral and cellular immune responses, VLPs have become a high-priority alternative to traditional vaccines against infectious pathogens. Creative Biolabs provides eVLP-based vaccine development services to help you discover potent vaccines against pathogenic enveloped viruses.

All of our products can only be used for research purposes. These vaccine ingredients CANNOT be used directly on humans or animals.