Next generation vaccines and vectors: Designing downstream processes for recombinant protein‐based virus‐like particles

Abstract

In recent years, the development of novel recombinant virus-like particles (VLPs) has been generating new perspectives for the prevention of untreated and arising infectious diseases. However, cost-reduction and acceleration of manufacturing processes for VLP-based vaccines or vectors are key challenges for the global health system. In particular, the design of rapid and cost-efficient purification processes is a critical bottleneck. In this review, we describe and evaluate new concepts, development strategies and unit operations for the downstream processing of VLPs. A special focus is placed on purity requirements and current trends, as well as chances and limitations of novel technologies. The discussed methods and case studies demonstrate the advances and remaining challenges in both rational process development and purification tools for large biomolecules. The potential of a new era of VLP-based products is highlighted by the progress of various VLPs in clinical phases.

Design of a hyperstable 60-subunit protein icosahedron

“…There has been considerable interest in repurposing such structures 3–5 , for example, virus-like particles for the targeted delivery and vaccine design. The ability to design proteins that self assemble into precisely specified, highly ordered icosahedral structures would open the door to a new generation of protein 'containers' that could exhibit properties custom-made for various applications.…”

Polysaccharide-based chromatographic adsorbents for virus purification and viral clearance

“…VLPs can be produced in a variety of cell culture systems including microbial (bacteria and yeasts, mainly Escherichia coli and Saccharomyces cerevisiae), insect (e.g., High Five™ cells from Trichoplusiani used in the Baculovirus Expression Vector System), mammalian (e.g., Chinese hamster ovary (CHO) cells) and -to a lesser extent-plant cells [16,17]. Therefore, both whole viruses and VLPs designed for vaccine formulations are derived from complex media containing biological impurities such as cell debris and host cell (HC)-derived contaminants (e.g., proteins, DNA, endotoxins), and their downstream processing must comply with strict purity requirements [13,14,20,21] detailed in regulatory guidelines [22]. Typical downstream production processes of viral particles involve three main steps (Fig.…”

“…Typical downstream purification processes of viral particles -whole viruses and VLPsfor biomedical applications include several chromatography unit operations separated or not by other concentration/purification procedures such as UF/DF [14,20,21]. Various examples of two-step chromatography procedures associating SEC and AEC [55-58], CEC [60,61] or HIC [52] for virus purification have already been mentioned.…”

Adjuvant formulations for virus-like particle (VLP) based vaccines

“…The VLP-based vaccines are not only particularly efficacious and safe, but also suitable for straightforward scalable manufacturing in an economically competitive manner [17]. In addition, VLP production can be achieved using current good manufacture practices (cGMP) without the need for the biological safety containment that is typically required for a live virus vaccine production process [33]. In the case of influenza, for example, new virus strains emerge due to the accumulation of mutations, (antigenic drift) [34] or by genetic reassortment, (antigenic shift) [35] resulting in epidemic outbreaks of recurring frequency and unpredictable intervals.…”