Bioengineering virus‐like particles as vaccines

Abstract

Virus-like particle (VLP) technology seeks to harness the optimally tuned immunostimulatory properties of natural viruses while omitting the infectious trait. VLPs that assemble from a single protein have been shown to be safe and highly efficacious in humans, and highly profitable. VLPs emerging from basic research possess varying levels of complexity and comprise single or multiple proteins, with or without a lipid membrane. Complex VLP assembly is traditionally orchestrated within cells using black-box approaches, which are appropriate when knowledge and control over assembly are limited. Recovery challenges including those of adherent and intracellular contaminants must then be addressed. Recent commercial VLPs variously incorporate steps that include VLP in vitro assembly to address these problems robustly, but at the expense of process complexity. Increasing research activity and translation opportunity necessitate bioengineering advances and new bioprocessing modalities for efficient and cost-effective production of VLPs. Emerging approaches are necessarily multi-scale and multi-disciplinary, encompassing diverse fields from computational design of molecules to new macro-scale purification materials. In this review, we highlight historical and emerging VLP vaccine approaches. We overview approaches that seek to specifically engineer a desirable immune response through modular VLP design, and those that seek to improve bioprocess efficiency through inhibition of intracellular assembly to allow optimal use of existing purification technologies prior to cell-free VLP assembly. Greater understanding of VLP assembly and increased interdisciplinary activity will see enormous progress in VLP technology over the coming decade, driven by clear translational opportunity.

Dendrimer-RNA nanoparticles generate protective immunity against lethal Ebola, H1N1 influenza, and Toxoplasma gondii challenges with a single dose

“…Importantly, generation of a new MDNP vaccine system composed of these dendrimers and replicon RNA takes only about 1 wk, in contrast to the cell culture and fertilized egg systems that can take 6 mo or more to develop (53)(54)(55)(56)(57)(58). In addition, postproduction purification required for this MDNP system is minimal, as is the risk of contaminating allergens relative to existing vaccine systems (59)(60)(61). Finally, this synthetic system is able to produce multiple antigens and to induce appropriate antibody and T-cell responses without additional adjuvants in a range of disease models.…”

Delivery strategies to enhance oral vaccination against enteric infections

“…The potential of these systems for oral vaccination is less clear but their efficacy could be enhanced by capsule based approaches with incorporated adjuvants. Other strategies that may offer potential include the expression of pathogen-derived antigens on live lactic acid bacteria (Lactobacillus casei and L. lactis) [109] and virus-like particles (VLPs) [110]. Components of toxins and toxoids have also been used to provide anti-toxic immunity.…”

“…Moreover, VLPs can be expressed with additional antigens on or, in the case of polysaccharide or lipid molecules, conjugated to the surface to create a multivalent vaccine [166,[169][170][171]. VLPs contain one or more viral capsid proteins which make up the protective outer shell of a virion and are usually expressed in a eukaryotic cell [110]. An example of a clinically and commercially viable VLP vaccine is the HepB vaccine [110], a product of the self-assembly of HepB surface antigen expressed in recombinant yeast cells [165].…”

“…VLPs contain one or more viral capsid proteins which make up the protective outer shell of a virion and are usually expressed in a eukaryotic cell [110]. An example of a clinically and commercially viable VLP vaccine is the HepB vaccine [110], a product of the self-assembly of HepB surface antigen expressed in recombinant yeast cells [165]. Another licensed VLP vaccine is the human papillomavirus (HPV) vaccine which was also the first prophylactic vaccine against a carcinogen [165].…”

Murine polyomavirus VLPs as a platform for cytotoxic T cell epitope-based influenza vaccine candidates

“…Firstly, native viral VLPs from pathogenic strains may be utilised by itself as vaccines. Secondly, chimeric VLPs carrying foreign antigens either by genetic engineering or chemical conjugation may be used as vaccines (Glasgow and Tullman-Ercek 2014;Kushnir et al 2012;Lua et al 2014;Rodriguez-Limas et al 2013;Yan et al 2015). VLPs are attractive for vaccine development not only because they are immunogenic, but also because they can be rapidly and efficiently produced (Yan et al 2015 (Gordon et al 1995;Otieno et al 2016).…”