Virus-like particles: the future of microbial factories and cell-free systems as platforms for vaccine development

Rodríguez-Limas, William A.; Sekar, Karthik; Tyo, Keith E.J.

doi:10.1016/j.copbio.2013.02.008

Cited by 98 publications

(80 citation statements)

References 52 publications

(51 reference statements)

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“…According to these studies, our VLP-based vaccine can induce better APC responses and stimulate humoral and cellular immunity. The Recombivax HB was the first VLP-based vaccine approved by FDA against hepatitis B (Bryan, 2007;Rodriguez-Limas et al, 2013). There are many VLP-based vaccines licensed for human and veterinary use (Landry et al, 2010;Kim et al, 2014;Landry et al, 2014).…”

Section: Groupsmentioning

confidence: 99%

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Innovation of a New Virus-Like Nanoparticle Vaccine System for the Specific Aerosol Relative Disease

Zhang

Tsai

Chao

et al. 2016

Aerosol Air Qual. Res.

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Human spend a lot of time indoors and indoor air quality (IAQ) has a great effect on quality of life in humans. Traditionally, bioaerosol in IAQs is focused on bacteria and fungus. Airborne viruses, particularly for the nanoparticletype virus, on the bioaerosol particulates are associated with the quality of human health in indoor environment. We establish the human like animal model, like pig, for testing the efficacy of the nano virus like particle (VLP) vaccine for aerosol relative disease. The porcine reproductive and respiratory syndrome virus (PRRSV), which is an airborne and a droplet infection virus coated on the small size of bioaerosol, carries a major infectious disease in the pig raising industry worldwide. There are commercial vaccines including attenuated and inactivated vaccines available, but their efficacy remains to be improved. VLP represents safe and effective vaccine platforms based on nano-technology. The fusion protein of capsid protein (Cap) from the porcine circovirus 2 (PCV2) and the glycoprotein 5 (GP5) from PRRSV were expressed by E. coli system. The fusion protein self-assembled with the GP5 to become a VLP nanoparticle. For testing, BALB/c mice were immunized with 10 µg of chimeric VLP nanoparticle once, which induced neutralization by antibody responses to PRRSV. The VLP nanoparticle vaccine induced high T cell proliferation, not evident in commercial vaccines tested on mice. Our results suggest that the cheaper VLP-based nanoparticle is a possibly viable approach model for specific airborne-relative-diseases human vaccine in the future.

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Section: Groupsmentioning

confidence: 99%

“…Most importantly, they are non-infectious, since they lack genetic contents (Schiller et al, 2012;Rodriguez-Limas et al, 2013). On the field of immunization, their safety is higher than that of attenuated vaccines, and also induces better humoral and cellular immune responses (Grgacic and Anderson, 2006;Roy and Noad, 2009).…”

Section: Introductionmentioning

confidence: 99%

Innovation of a New Virus-Like Nanoparticle Vaccine System for the Specific Aerosol Relative Disease

Zhang

Tsai

Chao

et al. 2016

Aerosol Air Qual. Res.

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“…It has an empty hollow, and does not contain other viral components such as pathogenic proteins and genetic materials, and is thus non-pathogenic and non-infectious Rodriguez-Limas et al 2013;Teunissen et al 2013). VLPs can either be enveloped or nonenveloped.…”

Section: The Murine Polyomavirus-like Particle Vaccine Delivery Technmentioning

confidence: 99%

“…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).…”

Section: The Murine Polyomavirus-like Particle Vaccine Delivery Technmentioning

confidence: 99%

“…Virus-like particles are generally derived from the coat proteins of a virus, which self-assemble into a spherical structure mimicking the original virus (hence its name) yet lacking DNA or RNA, rendering them non-infectious (Rodriguez-Limas et al 2013). They have been developed for various uses such as antigen carriers (Babin et al 2013;Kawano et al 2014;Wibowo et al 2012) or as carriers of other cargos such as drugs (Glasgow and Tullman-Ercek 2014), proteins (Abbing et al 2004), and both oligonucleotides and plasmid DNA (Braun et al 1999).…”

Section: Murine Polyoma Viral Coat Proteins As a Vaccine Delivery Systemmentioning

confidence: 99%

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

Abidin¹

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This research examined the ability of virus-like particles (VLP) assembled from the coat proteins of Murine polyomavirus (MPyV) to carry cytotoxic T cell (Tc) epitopes. MPyV VLPs can be assembled in vitro from purified subunits composed of pentamers of the major coat protein VP1 called capsomeres; and this approach provides fine control over VLP composition and structure. Tc-epitopes are often highly hydrophobic, which poses a significant bioengineering challenge and two distinct approaches were pursued to determine the optimal delivery strategy of Influenza Tc-epitopes by MPyV VLP. Firstly, identified epitopes were externally presented using established sites for peptide insertion on the MPyV major coat protein, VP1. Secondly, polypeptides possessing multiple epitopes were encapsidated within VP1 VLP using precise elements of the minor coat protein VP2/3 that interact with the interior cavity of capsomeres. Hydrophobicity-related capsomere aggregation arising from single Tc epitope presentation was successfully circumvented by engineering charged amino acids (DD) flanking the epitope displayed on a surface-exposed loop of VP1 and by use of an optimised buffer condition. A multiparametric, high-throughput buffer screen was implemented to optimise pH and buffer additives during affinity tag removal. Stable modified capsomere recovered from this reaction were assembly competent in the presence of L-Arginine, and VLP yield was high when modular capsomeres were co-assembled with unmodified VP1 capsomeres forming stable mosaic VLPs. The ability of the MPyV VLP to encapsidate foreign protein was first evaluated and optimised with green fluorescent protein (GFP) as a model protein to enable monitoring and analysis.A minimal VP1-interacting sequence was defined from the carboxy-terminus of VP2/3 (VP2C) and fused to the amino-terminus of GFP, ensuring internalisation of the reporter protein. VP1:VP2C-GFP capsomere complexes were successfully recovered when VP1 was co-expressed with VP2C-GFP, whereas complex formation was not observed when VP1 and VP2C-GFP were mixed in vitro.Recovered capsomere complexes were assembly competent and amount of encapsidated GFP was controllable when VP1:VP2C-GFP capsomere complexes were co-assembled with unmodified VP1 capsomeres in a defined molar ratio. The encapsidation approach was then applied to a subdomain of the Influenza matrix protein M1 by co-expressing VP1 with VP2C-M1-I. M1-I capsomere complexes were assembly competent as indicated by gel electrophoresis, dynamic light scattering, and transmission electron microscopy. To enable recovery of VLPs for analysis and characterisation as well as to confirm encapsidation and the formation of mosaic VLPs, a semi-preparative size exclusion chromatography method was developed. This research was able to address bioengineering challenges posed by hydrophobic epitope presentation and developed MPyV

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Blocking endocytotic mechanisms to improve heterologous protein titers in Saccharomyces cerevisiae

Rodríguez-Limas

Tannenbaum

Tyo

2014

Biotech & Bioengineering

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Saccharomyces cerevisiae is a useful platform for protein production of biopharmaceuticals and industrial enzymes. To date, substantial effort has focused on alleviating several bottlenecks in expression and the secretory pathway. Recently, it has been shown that highly active endocytosis could decrease the overall protein titer in the supernatant. In this study, we block endocytosis and trafficking to the vacuole using a modified TEV Protease-Mediated Induction of Protein Instability (mTIPI) system to disrupt the endocytotic and vacuolar complexes. We report that conditional knock-down of endocytosis gene Rvs161 improved the concentration of α-amylase in supernatant of S. cerevisiae cultures by 63.7% compared to controls. By adaptive evolution, we obtained knock-down mutants in Rvs161 and End3 genes with 2-fold and 3-fold α-amylase concentrations compared to controls that were not evolved. Our study demonstrates that genetic blocking of endocytotic mechanisms can improve heterologous protein production in S. cerevisiae. This result is likely generalizable to other eukaryotic secretion hosts.

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Virus-like particles: the future of microbial factories and cell-free systems as platforms for vaccine development

Cited by 98 publications

References 52 publications

Innovation of a New Virus-Like Nanoparticle Vaccine System for the Specific Aerosol Relative Disease

Innovation of a New Virus-Like Nanoparticle Vaccine System for the Specific Aerosol Relative Disease

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

Blocking endocytotic mechanisms to improve heterologous protein titers in Saccharomyces cerevisiae

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