Platforms, advances, and technical challenges in virus-like particles-based vaccines

Abstract

Viral infectious diseases threaten human health and global stability. Several vaccine platforms, such as DNA, mRNA, recombinant viral vectors, and virus-like particle-based vaccines have been developed to counter these viral infectious diseases. Virus-like particles (VLP) are considered real, present, licensed and successful vaccines against prevalent and emergent diseases due to their non-infectious nature, structural similarity with viruses, and high immunogenicity. However, only a few VLP-based vaccines have been commercialized, and the others are either in the clinical or preclinical phases. Notably, despite success in the preclinical phase, many vaccines are still struggling with small-scale fundamental research owing to technical difficulties. Successful production of VLP-based vaccines on a commercial scale requires a suitable platform and culture mode for large-scale production, optimization of transduction-related parameters, upstream and downstream processing, and monitoring of product quality at each step. In this review article, we focus on the advantages and disadvantages of various VLP-producing platforms, recent advances and technical challenges in VLP production, and the current status of VLP-based vaccine candidates at commercial, preclinical, and clinical levels.

Virus‐like particles as powerful vaccination strategy against human viruses

“…170 This issue can be avoided by the use of either bubble-free systems or nonionic copolymers depending on the sensitivity levels of the cells. 9 Large-scale production and purification of VLPs are associated with the presence of contaminants, which can generate undesirable side effects in vaccinated persons. 171 Therefore, further treatments (i.e., density gradients or even chromatography) may be needed to diminish unwanted impurities levels.…”

“…19,41 The mammalian cells platform offers an important advantage over other ESs in that can make complex and precise PTMs for proper protein folding. 9 However, mammalian cell culture has potential drawbacks, including (a) High cost of production, (b) long-expression time, (c) low controllability, and (d) viral contamination risk. 49,55 This expression platform has been used to produce various VLPs against Middle East respiratory syndrome expressed in Huh7 cells 56 and IVs using HEK293; vero; or CHO mammalian cells.…”

“…Moreover, they support eukaryotic protein PTMs 44 . The B/IC ES is suitable for producing vaccines against viruses that evolve rapidly between outbreaks following changes in their surface proteins, such as IVs 9,41 . Producing an influenza VLP‐based vaccine in a B/IC platform may be completed in 6 weeks approximately after identifying the circulating strain during the flu season 47 .…”

“…The genetic fusion of the sequences of single or multiple structural capsid proteins into VLPs inside appropriate production systems or in cell‐free conditions can sometimes be challenging, as VLPs may lose their self‐assembly characteristic or cause incorrect folding process, resulting in the formation of damaged VLPs 24,166 . Time‐intensive planning and optimization processes are required for appropriate antigen assembly 9,167 …”

Nucleic Acid Delivery Nanotechnologies for In Vivo Cell Programming

“…53,54 The virus-resembling structures of VLPs can be either formed from viral protein capsids/lipid envelopes or cytosolic viral proteins from one or more viruses like human immunodeficiency virus, bacteriophages, and hepatitis C virus (HCV). 54,55 Due to the presence of viral glycoproteins on the VLP surface, and their nanometer size range (20−200 nm), VLPs can retain similar cell and tissue tropisms as their viral vector counterparts and can easily penetrate tissues, thereby supplying an effective platform for targeted cargo delivery. 54,56 The highly dense multivalent display of epitopes on the surface of VLPs also makes them immunogenic in nature, which means they can induce both humoral and cellular immune responses with no risk of viral replication in the host system due to the absence of infectious genetic material.…”