Synthetic biology for bioengineering virus‐like particle vaccines

Abstract

Vaccination is the most effective method of disease prevention and control. Many viruses and bacteria that once caused catastrophic pandemics (e.g., smallpox, poliomyelitis, measles, and diphtheria) are either eradicated or effectively controlled through routine vaccination programs. Nonetheless, vaccine manufacturing remains incredibly challenging. Viruses exhibiting high antigenic diversity and high mutation rates cannot be fairly contested using traditional vaccine production methods and complexities surrounding the manufacturing processes, which impose significant limitations. Virus-like particles (VLPs) are recombinantly produced viral structures that exhibit immunoprotective traits of native viruses but are noninfectious. SeveralVLPs that compositionally match a given natural virus have been developed and licensed as vaccines. Expansively, a plethora of studies now confirms that VLPs can be designed to safely present heterologous antigens from a variety of pathogens unrelated to the chosen carrier VLPs. Owing to this design versatility, VLPs offer technological opportunities to modernize vaccine supply and disease response through rational bioengineering. These opportunities are greatly enhanced with the application of synthetic biology, the redesign and construction of novel biological entities. This review outlines how synthetic biology is currently applied to engineer VLP functions and manufacturing process. Current and developing technologies for the identification of novel target-specific antigens and their usefulness for rational engineering of VLP functions (e.g., presentation of structurally diverse antigens, enhanced antigen immunogenicity, and improved vaccine stability) are described.When applied to manufacturing processes, synthetic biology approaches can also overcome specific challenges in VLP vaccine production. Finally, we address several challenges and benefits associated with the translation of VLP vaccine development into the industry. K E Y W O R D S

Quantification of the HIV‐1 virus‐like particle production process by super‐resolution imaging: From VLP budding to nanoparticle analysis

“…Their success as immunogens and nanocarriers has been demonstrated in numerous preclinical and clinical trials over the last years (Charlton Hume et al, 2019). Among the different VLP candidates, enveloped human immunodeficiency virus‐1 (HIV‐1) Gag VLPs are in the spotlight as a scaffold for antigen presentation against different diseases (Cervera et al, 2019; Charlton Hume et al, 2019) and as a reference material for the production of extracellular vesicles (EVs; Geeurickx et al, 2019). The HIV‐1 structural polyprotein (Gag) has the capacity to form noninfective viral particles on their own (Göttlinger, 2001).…”

Bioengineered Polyhydroxyalkanoates as Immobilized Enzyme Scaffolds for Industrial Applications

“…Virus-like particles consist of the viral capsid proteins (CPs; Charlton Hume et al, 2019). The formation of VLPs is a selfassembling process of the viral capsid, which potentially mimics the general structure of the parental virus.…”

“…The formation of VLPs is a selfassembling process of the viral capsid, which potentially mimics the general structure of the parental virus. However, VLPs do not contain nucleic acids, and, thus, there is no risk of causing infection (Charlton Hume et al, 2019;Janitzek et al, 2019). The CP subunits can be genetically modified for bioconjugation, enabling molecules of interest to be densely displayed or encapsulated in homogeneous spatial orientation (Tan and Jiang, 2017;Charlton Hume et al, 2019).…”

“…However, VLPs do not contain nucleic acids, and, thus, there is no risk of causing infection (Charlton Hume et al, 2019;Janitzek et al, 2019). The CP subunits can be genetically modified for bioconjugation, enabling molecules of interest to be densely displayed or encapsulated in homogeneous spatial orientation (Tan and Jiang, 2017;Charlton Hume et al, 2019). VLPs have made significant advances in various fields, from vaccinology to industrial uses due to their promising characteristics, including monodispersed particle size distribution, defined geometric surfaces, biosafety, and functional programmability (Mohsen et al, 2017;Janitzek et al, 2019).…”

“…A significant drawback of the VLP platform is that the size of the protein attached to, or accommodated within, the particles is limited. This disadvantage precludes the presentation of large functional moieties (Charlton Hume et al, 2019).…”