The True Story and Advantages of RNA Phage Capsids as Nanotools

Abstract

RNA phages are often used as prototypes for modern recombinant virus-like particle (VLP) technologies. Icosahedral RNA phage VLPs can be formed from coat proteins (CPs) and are efficiently produced in bacteria and yeast. Both genetic fusion and chemical coupling have been successfully used for the production of numerous chimeras based on RNA phage VLPs. In this review, we describe advances in RNA phage VLP technology along with the history of the Leviviridae family, including its taxonomical organization, genomic structure, and important role in the development of molecular biology. Comparative 3D structures of different RNA phage VLPs are used to explain the level of VLP tolerance to foreign elements displayed on VLP surfaces. We also summarize data that demonstrate the ability of CPs to tolerate different organic (peptides, oligonucleotides, and carbohydrates) and inorganic (metal ions) compounds either chemically coupled or noncovalently added to the outer and/or inner surfaces of VLPs. Finally, we present lists of nanotechnological RNA phage VLP applications, such as experimental vaccines constructed by genetic fusion and chemical coupling methodologies, nanocontainers for targeted drug delivery, and bioimaging tools.

Target highlights from the first post‐PSI CASP experiment (CASP12, May–August 2016)

“…ssRNA phages like MS2, Qβ and AP205 infect various gram‐negative bacteria and are among the simplest known viruses used for decades as models to study various problems in molecular biology. Lately, ssRNA phages and their components have found several applications, notably in vaccine development . Capsid of ssRNA phages contains 178 copies of coat protein (CP) and a single copy of maturation protein, responsible for attachment of phage particles to bacterial receptor .…”

“…To avoid pre‐existing immune responses, pathogens that do not target humans are preferable as carriers of antigens. For this purpose, VLPs of ssRNA phages like MS2, Qβ, and AP205 have been widely used …”

Advantages and Prospects of Tag/Catcher Mediated Antigen Display on Capsid-Like Particle-Based Vaccines

“…Several features of the AP205 CLP make it attractive as a vaccine backbone, including its structure, intrinsic immunogenicity and manufacturability [73,74]. While the overall capsid structure within the RNA bacteriophage family is similar, the surface exposed regions available for genetic fusion differ substantially [74,75]. The AP205 capsid is remarkable in that both the N-and C-termini are surface exposed and evenly distributed on the assembled CLP [74].…”

Peer Review #3 of "Application of built-in adjuvants for epitope-based vaccines (v0.1)"

“…Recent reports have shown that the Qβ bacteriophage contains TLR ligands that can enhance Qβ-VLP-induced T cellindependent and -dependent Ab reactions, including a germinal center (GC) reaction via of TLR/MyD88 signaling in B cells (Tian et al, 2018). This VLP platform which contains no viral genome can be used in the future as a carrier system for the administration of safe vaccines against many pathogens (Pumpens et al, 2016 Manuscript to be reviewed the envelope proteins of Zika virus on the surface of a highly immunogenic bacteriophage VLP platform (MS2, PP7, and Qβ), and evaluated the immunogenicity of these VLPs in mice (Basu et al, 2018) Zhai et al also displayed consensus peptides from HPV L2 and tandem HPV31/16L2 peptides on the surface of bacteriophage MS2 VLPs. These MS2-L2 VLPs can induce high antibody titers in mice and are cost-effective vaccine candidates against HPV; however, HPV vaccines with greater cross-protection should be further evaluated to prevent more types of HPV (Zhai et al, 2017).…”