Virus-like particle

Last updated

Virus-like particles (VLPs) are molecules that closely resemble viruses, but are non-infectious because they contain no viral genetic material. They can be naturally occurring or synthesized through the individual expression of viral structural proteins, which can then self assemble into the virus-like structure. [1] [2] [3] [4] Combinations of structural capsid proteins from different viruses can be used to create recombinant VLPs. Both in-vivo assembly (i.e., assembly inside E. coli bacteria via recombinant co-expression of multiple proteins) and in-vitro assembly (i.e., protein self-assembly in a reaction vessel using stoichiometric quantities of previously purified proteins) have been successfully shown to form virus-like particles. VLPs derived from the Hepatitis B virus (HBV) and composed of the small HBV derived surface antigen (HBsAg) were described in 1968 from patient sera. [5] VLPs have been produced from components of a wide variety of virus families including Parvoviridae (e.g. adeno-associated virus), Retroviridae (e.g. HIV), Flaviviridae (e.g. Hepatitis C virus), Paramyxoviridae (e.g. Nipah) and bacteriophages (e.g. Qβ, AP205). [1] VLPs can be produced in multiple cell culture systems including bacteria, mammalian cell lines, insect cell lines, yeast and plant cells. [6] [7]

Contents

VLPs can also refer to structures produced by some LTR retrotransposons (under Ortervirales) in nature. These are defective, immature virions, sometimes containing genetic material, that are generally non-infective due to the lack of a functional viral envelope. [8] [9] In addition, wasps produce polydnavirus vectors with pathogenic genes (but not core viral genes) or gene-less VLPs to help control their host. [10] [11]

Applications

This diagram shows how surrogate viruses expressing the SARS-CoV-2 spike protein can be used to measure the activity of neutralizing antibodies that target the spike protein and prevent the virus from entering host cells. 238054 web surrogate viruses.jpg
This diagram shows how surrogate viruses expressing the SARS-CoV-2 spike protein can be used to measure the activity of neutralizing antibodies that target the spike protein and prevent the virus from entering host cells.

Therapeutic and imaging agents

VLPs are a candidate delivery system for genes or other therapeutics. [12] These drug delivery agents have been shown to effectively target cancer cells in vitro. [13] It is hypothesized that VLPs may accumulate in tumor sites due to the enhanced permeability and retention effect, which could be useful for drug delivery or tumor imaging. [14]

Vaccines

VLPs are useful as vaccines. VLPs contain repetitive, high density displays of viral surface proteins that present conformational viral epitopes that can elicit strong T cell and B cell immune responses. [15] The particles' small radius of roughly 20-200 nm allows sufficient draining into lymph nodes. Since VLPs cannot replicate, they provide a safer alternative to attenuated viruses. VLPs were used to develop FDA-approved vaccines for Hepatitis B and human papillomavirus, which are commercially available. [16]

A selection of viruslike particle-based vaccines against human papilloma virus (HPV) such as Cervarix by GlaxoSmithKline along with Gardasil and Gardasil-9, are available, produced by Merck & Co. Gardasil consists of recombinant VLPs assembled from the L1 proteins of HPV types 6, 11, 16, and 18 expressed in yeast. It is adjuvanted with aluminum hydroxyphosphate sulfate. Gardasil-9 consists of L1 epitopes of 31, 33, 45, 52 and 58 in addition to the listed L1 epitopes found in Gardasil. Cervarix consists of recombinant VLPs assembled from the L1 proteins of HPV types 16 and 18, expressed in insect cells, and is adjuvanted with 3-O-Desacyl-4-monophosphoryl lipid (MPL) A and aluminum hydroxide. [17]

The first VLP vaccine that addresses malaria, Mosquirix, (RTS,S) has been approved by EU regulators. It was expressed in yeast. RTS,S is a portion of the Plasmodium falciparum circumsporozoite protein fused to the Hepatitis B surface antigen (RTS), combined with Hepatitis B surface antigen (S), and adjuvanted with AS01 (consisting of (MPL)A and saponin).

Vaccine production can begin as soon as the virus strain is sequenced and can take as little as 12 weeks, compared to 9 months for traditional vaccines. In early clinical trials, VLP vaccines for influenza appeared to provide complete protection against both the Influenza A virus subtype H5N1 and the 1918 flu pandemic. [18] Novavax and Medicago Inc. have run clinical trials of their VLP flu vaccines. [19] [20] Several VLP vaccines for COVID-19, including Novavax, are under development. [16] [21]

VLPs have been used to develop a pre-clinical vaccine candidate against chikungunya virus. [15]

Bio-inspired Material Synthesis

Compartmentalization is a common theme in biology. Nature is full of examples of hierarchically compartmentalized multicomponent structures that self-assembles from individual building blocks. Taking inspiration from nature, synthetic approaches using polymers, phase-separated microdroplets, lipids and proteins have been used to mimic hierarchical compartmentalization of natural systems and to form functional bio-inspired nanomaterials. [22] [23] [24] For example, protein self-assembly was used to encapsulate multiple copies of ferritin protein cages as sub-compartments inside P22 virus-like particle as larger compartment essentially forming a Matryoshka-like nested cage-within-cage structure. [25] The authors further demonstrated stoichiometric encapsulation of cellobiose-hydrolysing β-glycosidase enzyme CelB along with ferritin protein cages using in-vitro self-assembly strategy to form multi-compartment cell-inspired protein cage structure. Using similar strategy, glutathione biosynthesizing enzymes were encapsulated inside bacteriophage P22 virus-like particles. [26] In a separate research, 3.5 nm small Cytochrome C with peroxidase-like activity was encapsulated inside a 9 nm small Dps protein cage to form organelle-inspired protein cage structure. [27]

Lipoparticle technology

The VLP lipoparticle was developed to aid the study of integral membrane proteins. [28] Lipoparticles are stable, highly purified, homogeneous VLPs that are engineered to contain high concentrations of a conformationally intact membrane protein of interest. Integral Membrane proteins are involved in diverse biological functions and are targeted by nearly 50% of existing therapeutic drugs. However, because of their hydrophobic domains, membrane proteins are difficult to manipulate outside of living cells. Lipoparticles can incorporate a wide variety of structurally intact membrane proteins, including G protein-coupled receptors (GPCR)s, ion channels and viral Envelopes. Lipoparticles provide a platform for numerous applications including antibody screening, production of immunogens and ligand binding assays. [29] [30]

Assembly

The understanding of self-assembly of VLPs was once based on viral assembly. This is rational as long as the VLP assembly takes place inside the host cell (in vivo), though the self-assembly event was found in vitro from the very beginning of the study about viral assembly. [31] Study also reveals that in vitro assembly of VLPs competes with aggregation [32] and certain mechanisms exist inside the cell to prevent the formation of aggregates while assembly is ongoing. [33]

Linking targeting groups to VLP surfaces

Attaching proteins, nucleic acids, or small molecules to the VLP surface, such as for targeting a specific cell type or for raising an immune response is useful. In some cases a protein of interest can be genetically fused to the viral coat protein. [34] However, this approach sometimes leads to impaired VLP assembly and has limited utility if the targeting agent is not protein-based. An alternative is to assemble the VLP and then use chemical crosslinkers, [35] reactive unnatural amino acids [36] or SpyTag/SpyCatcher reaction [37] [38] in order to covalently attach the molecule of interest. This method is effective at directing the immune response against the attached molecule, thereby inducing high levels of neutralizing antibody and even being able to break tolerance to self-proteins displayed on VLPs. [38]

Related Research Articles

<span class="mw-page-title-main">DNA vaccine</span> Vaccine containing DNA

A DNA vaccine is a type of vaccine that transfects a specific antigen-coding DNA sequence into the cells of an organism as a mechanism to induce an immune response.

<i>Hepadnaviridae</i> Family of viruses

Hepadnaviridae is a family of viruses. Humans, apes, and birds serve as natural hosts. There are currently 18 species in this family, divided among 5 genera. Its best-known member is hepatitis B virus. Diseases associated with this family include: liver infections, such as hepatitis, hepatocellular carcinomas, and cirrhosis. It is the sole accepted family in the order Blubervirales.

<span class="mw-page-title-main">Hemagglutinin (influenza)</span> Hemagglutinin of influenza virus

Influenza hemagglutinin (HA) or haemagglutinin[p] is a homotrimeric glycoprotein found on the surface of influenza viruses and is integral to its infectivity.

<span class="mw-page-title-main">Viral protein</span>

The term viral protein refers to both the products of the genome of a virus and any host proteins incorporated into the viral particle. Viral proteins are grouped according to their functions, and groups of viral proteins include structural proteins, nonstructural proteins, regulatory proteins, and accessory proteins. Viruses are non-living and do not have the means to reproduce on their own, instead depending on their host cell's machinery to do this. Thus, viruses do not code for most of the proteins required for their replication and the translation of their mRNA into viral proteins, but use proteins encoded by the host cell for this purpose.

<span class="mw-page-title-main">Original antigenic sin</span> Immune phenomenon

Original antigenic sin, also known as antigenic imprinting, the Hoskins effect, immunological imprinting, or primary addiction is the propensity of the immune system to preferentially use immunological memory based on a previous infection when a second slightly different version of that foreign pathogen is encountered. This leaves the immune system "trapped" by the first response it has made to each antigen, and unable to mount potentially more effective responses during subsequent infections. Antibodies or T-cells induced during infections with the first variant of the pathogen are subject to repertoire freeze, a form of original antigenic sin.

Duck hepatitis B virus, abbreviated DHBV, is part of the genus Avihepadnavirus of the Hepadnaviridae, and is the causal agent of duck hepatitis B.

<span class="mw-page-title-main">Viral envelope</span> Outermost layer of many types of the infectious agent

A viral envelope is the outermost layer of many types of viruses. It protects the genetic material in their life cycle when traveling between host cells. Not all viruses have envelopes. A viral envelope protein or E protein is a protein in the envelope, which may be acquired by the capsid from an infected host cell.

<span class="mw-page-title-main">Virus</span> Infectious agent that replicates in cells

A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Viruses are found in almost every ecosystem on Earth and are the most numerous type of biological entity. Since Dmitri Ivanovsky's 1892 article describing a non-bacterial pathogen infecting tobacco plants and the discovery of the tobacco mosaic virus by Martinus Beijerinck in 1898, more than 11,000 of the millions of virus species have been described in detail. The study of viruses is known as virology, a subspeciality of microbiology.

<span class="mw-page-title-main">Hepatitis C virus envelope glycoprotein E1</span>

E1 is one of two subunits of the envelope glycoprotein found in the hepatitis C virus. The other subunit is E2. This protein is a type 1 transmembrane protein with a highly glycosylated N-terminal ectodomain and a C-terminal hydrophobic anchor. After being synthesized the E1 glycoproteins associates with the E2 glycoprotein as a noncovalent heterodimer.

A hepatitis C vaccine, a vaccine capable of protecting against the hepatitis C virus (HCV), is not yet available. Although vaccines exist for hepatitis A and hepatitis B, development of an HCV vaccine has presented challenges. No vaccine is currently available, but several vaccines are currently under development.

A subunit vaccine is a vaccine that contains purified parts of the pathogen that are antigenic, or necessary to elicit a protective immune response. Subunit vaccine can be made from dissembled viral particles in cell culture or recombinant DNA expression, in which case it is a recombinant subunit vaccine.

<i>Hepatitis B virus</i> Species of the genus Orthohepadnavirus

Hepatitis B virus (HBV) is a partially double-stranded DNA virus, a species of the genus Orthohepadnavirus and a member of the Hepadnaviridae family of viruses. This virus causes the disease hepatitis B.

A neutralizing antibody (NAb) is an antibody that defends a cell from a pathogen or infectious particle by neutralizing any effect it has biologically. Neutralization renders the particle no longer infectious or pathogenic. Neutralizing antibodies are part of the humoral response of the adaptive immune system against viruses, intracellular bacteria and microbial toxin. By binding specifically to surface structures (antigen) on an infectious particle, neutralizing antibodies prevent the particle from interacting with its host cells it might infect and destroy.

<i>Lagovirus</i> Genus of viruses

Lagovirus is a genus of viruses, in the family Caliciviridae. Lagomorphs serve as natural hosts. There are two species in this genus. Diseases associated with this genus include: necrotizing hepatitis leading to fatal hemorrhages.

Peptide-based synthetic vaccines are subunit vaccines made from peptides. The peptides mimic the epitopes of the antigen that triggers direct or potent immune responses. Peptide vaccines can not only induce protection against infectious pathogens and non-infectious diseases but also be utilized as therapeutic cancer vaccines, where peptides from tumor-associated antigens are used to induce an effective anti-tumor T-cell response.

<span class="mw-page-title-main">Murine polyomavirus</span> Species of virus

Murine polyomavirus is an unenveloped double-stranded DNA virus of the polyomavirus family. The first member of the family discovered, it was originally identified by accident in the 1950s. A component of mouse leukemia extract capable of causing tumors, particularly in the parotid gland, in newborn mice was reported by Ludwik Gross in 1953 and identified as a virus by Sarah Stewart and Bernice Eddy at the National Cancer Institute, after whom it was once called "SE polyoma". Stewart and Eddy would go on to study related polyomaviruses such as SV40 that infect primates, including humans. These discoveries were widely reported at the time and formed the early stages of understanding of oncoviruses.

<span class="mw-page-title-main">Major capsid protein VP1</span>

Major capsid protein VP1 is a viral protein that is the main component of the polyomavirus capsid. VP1 monomers are generally around 350 amino acids long and are capable of self-assembly into an icosahedral structure consisting of 360 VP1 molecules organized into 72 pentamers. VP1 molecules possess a surface binding site that interacts with sialic acids attached to glycans, including some gangliosides, on the surfaces of cells to initiate the process of viral infection. The VP1 protein, along with capsid components VP2 and VP3, is expressed from the "late region" of the circular viral genome.

Flock House virus (FHV) is in the Alphanodavirus genus of the Nodaviridae family of viruses. Flock House virus was isolated from a grass grub at the Flock House research station in Bulls, New Zealand. FHV is an extensively studied virus and is considered a model system for the study of other non-enveloped RNA viruses owing to its small size and genetic tractability, particularly to study the role of the transiently exposed hydrophobic gamma peptide and the metastability of the viral capsid. FHV can be engineered in insect cell culture allowing for the tailored production of native or mutant authentic virions or virus-like-particles. FHV is a platform for nanotechnology and nanomedicine, for example, for epitope display and vaccine development. Viral entry into host cells occurs via receptor-mediated endocytosis. Receptor binding initiates a sequence of events during which the virus exploits the host environment in order to deliver the viral cargo in to the host cytosol. Receptor binding prompts the meta-stability of the capsid–proteins, the coordinated rearrangements of which are crucial for subsequent steps in the infection pathway. In addition, the transient exposure of a covalently-independent hydrophobic γ-peptide is responsible for breaching cellular membranes and is thus essential for the viral entry of FHV into host cells.

Virus nanotechnology is the use of viruses as a source of nanoparticles for biomedical purposes. Viruses are made up of a genome and a capsid; and some viruses are enveloped. Most virus capsids measure between 20-500 nm in diameter. Because of their nanometer size dimensions, viruses have been considered as naturally occurring nanoparticles. Virus nanoparticles have been subject to the nanoscience and nanoengineering disciplines. Viruses can be regarded as prefabricated nanoparticles. Many different viruses have been studied for various applications in nanotechnology: for example, mammalian viruses are being developed as vectors for gene delivery, and bacteriophages and plant viruses have been used in drug delivery and imaging applications as well as in vaccines and immunotherapy intervention.

Bacteriophage AP205 is a plaque-forming bacteriophage that infects Acinetobacter bacteria. Bacteriophage AP205 is a protein-coated virus with a positive single-stranded RNA genome. It is a member of the family Fiersviridae, consisting of particles that infect Gram-negative bacteria such as E. coli.

References

  1. 1 2 Zeltins A (January 2013). "Construction and characterization of virus-like particles: a review". Molecular Biotechnology. 53 (1): 92–107. doi:10.1007/s12033-012-9598-4. PMC   7090963 . PMID   23001867.
  2. ↑ Buonaguro L, Tagliamonte M, Tornesello ML, Buonaguro FM (November 2011). "Developments in virus-like particle-based vaccines for infectious diseases and cancer". Expert Review of Vaccines. 10 (11): 1569–83. doi:10.1586/erv.11.135. PMID   22043956. S2CID   25513040.
  3. ↑ "NCI Dictionary of Cancer Terms". National Cancer Institute. 2011-02-02. Retrieved 2019-04-19.
  4. ↑ Mohsen MO, Gomes AC, Vogel M, Bachmann MF (July 2018). "Interaction of Viral Capsid-Derived Virus-Like Particles (VLPs) with the Innate Immune System". Vaccines. 6 (3): 37. doi: 10.3390/vaccines6030037 . PMC   6161069 . PMID   30004398.
  5. ↑ Bayer ME, Blumberg BS, Werner B (June 1968). "Particles associated with Australia antigen in the sera of patients with leukaemia, Down's Syndrome and hepatitis". Nature. 218 (5146): 1057–9. Bibcode:1968Natur.218.1057B. doi:10.1038/2181057a0. PMID   4231935. S2CID   39890704.
  6. ↑ Santi L, Huang Z, Mason H (September 2006). "Virus-like particles production in green plants". Methods. 40 (1): 66–76. doi:10.1016/j.ymeth.2006.05.020. PMC   2677071 . PMID   16997715.
  7. ↑ Huang X, Wang X, Zhang J, Xia N, Zhao Q (2017-02-09). "Escherichia coli-derived virus-like particles in vaccine development". npj Vaccines. 2 (1): 3. doi:10.1038/s41541-017-0006-8. PMC   5627247 . PMID   29263864.
  8. ↑ Beliakova-Bethell N, Beckham C, Giddings TH, Winey M, Parker R, Sandmeyer S (January 2006). "Virus-like particles of the Ty3 retrotransposon assemble in association with P-body components". RNA. 12 (1): 94–101. doi:10.1261/rna.2264806. PMC   1370889 . PMID   16373495.
  9. ↑ Purzycka KJ, Legiewicz M, Matsuda E, Eizentstat LD, Lusvarghi S, Saha A, et al. (January 2013). "Exploring Ty1 retrotransposon RNA structure within virus-like particles". Nucleic Acids Research. 41 (1): 463–73. doi:10.1093/nar/gks983. PMC   3592414 . PMID   23093595.
  10. ↑ Burke, Gaelen R.; Strand, Michael R. (2012-01-31). "Polydnaviruses of Parasitic Wasps: Domestication of Viruses To Act as Gene Delivery Vectors". Insects. 3 (1): 91–119. doi: 10.3390/insects3010091 . PMC   4553618 . PMID   26467950.
  11. ↑ Leobold, Matthieu; Bézier, Annie; Pichon, Apolline; Herniou, Elisabeth A; Volkoff, Anne-Nathalie; Drezen, Jean-Michel; Abergel, Chantal (July 2018). "The Domestication of a Large DNA Virus by the Wasp Venturia canescens Involves Targeted Genome Reduction through Pseudogenization". Genome Biology and Evolution. 10 (7): 1745–1764. doi: 10.1093/gbe/evy127 . PMC   6054256 . PMID   29931159.
  12. ↑ Petry H, Goldmann C, Ast O, Lüke W (October 2003). "The use of virus-like particles for gene transfer". Current Opinion in Molecular Therapeutics. 5 (5): 524–8. PMID   14601522.
  13. ↑ Galaway, F. A. & Stockley, P. G. MS2 viruslike particles: A robust, semisynthetic targeted drug delivery platform. Mol. Pharm. 10, 59–68 (2013).
  14. ↑ Kovacs, E. W. et al. Dual-surface-modified bacteriophage MS2 as an ideal scaffold for a viral capsid-based drug delivery system. Bioconjug. Chem. 18, 1140–1147 (2007).
  15. 1 2 Akahata W, Yang ZY, Andersen H, Sun S, Holdaway HA, Kong WP, et al. (March 2010). "A virus-like particle vaccine for epidemic Chikungunya virus protects nonhuman primates against infection". Nature Medicine. 16 (3): 334–8. doi:10.1038/nm.2105. PMC   2834826 . PMID   20111039.
  16. 1 2 Hotez, Peter J.; Bottazzi, Maria Elena (27 January 2022). "Whole Inactivated Virus and Protein-Based COVID-19 Vaccines". Annual Review of Medicine. 73 (1): 55–64. doi: 10.1146/annurev-med-042420-113212 . ISSN   0066-4219. PMID   34637324. S2CID   238747462 . Retrieved 14 April 2022.
  17. ↑ Zhang X, Xin L, Li S, Fang M, Zhang J, Xia N, Zhao Q (2015). "Lessons learned from successful human vaccines: Delineating key epitopes by dissecting the capsid proteins". Human Vaccines & Immunotherapeutics. 11 (5): 1277–92. doi:10.1080/21645515.2015.1016675. PMC   4514273 . PMID   25751641.
  18. ↑ Perrone LA, Ahmad A, Veguilla V, Lu X, Smith G, Katz JM, et al. (June 2009). "Intranasal vaccination with 1918 influenza virus-like particles protects mice and ferrets from lethal 1918 and H5N1 influenza virus challenge". Journal of Virology. 83 (11): 5726–34. doi:10.1128/JVI.00207-09. PMC   2681940 . PMID   19321609.
  19. ↑ John Gever (12 September 2010). "ICAAC: High Antibody Titers Seen With Novel Flu Vaccine".
  20. ↑ Landry N, Ward BJ, Trépanier S, Montomoli E, Dargis M, Lapini G, Vézina LP (December 2010). Fouchier RA (ed.). "Preclinical and clinical development of plant-made virus-like particle vaccine against avian H5N1 influenza". PLOS ONE. 5 (12): e15559. Bibcode:2010PLoSO...515559L. doi: 10.1371/journal.pone.0015559 . PMC   3008737 . PMID   21203523.
  21. ↑ Leo L (27 March 2021). "Hope to launch Covovax by September, says Serum Institute CEO". mint. Archived from the original on 13 May 2021. Retrieved 28 March 2021.
  22. ↑ ang, T.-Y. D.; Hak, C. R. C.; Thompson, A. J.; Kuimova, M.K.; Williams, D. S.; Perriman, A. W.; Mann, S. Fatty acid membraneassembly on coacervate microdroplets as a step towards a hybridprotocell model.Nat. Chem.2014,6, 527−533.
  23. ↑ Marguet, M.; Sandre, O.; Lecommandoux, S. Polymersomes in“gelly”polymersomes: toward structural cell mimicry.Langmuir2012,28, 2035−2043.
  24. ↑ alker, S. A.; Kennedy, M. T.; Zasadzinski, J. A. Encapsulationof bilayer vesicles by self-assembly.Nature1997,387,61−64.
  25. ↑ Waghwani HK, Uchida M, Douglas, T (April 2020). "Virus-Like Particles (VLPs) as a Platform for HierarchicalCompartmentalization". Biomacromolecules. 21 (6): 2060–2072. doi: 10.1021/acs.biomac.0c00030 . PMID   32319761.
  26. ↑ Wang Y, Uchida M, Waghwani HK, Douglas, T (December 2020). "Synthetic Virus-like Particles for Glutathione Biosynthesis". ACS Synthetic Biology. 9 (12): 3298–3310. doi:10.1021/acssynbio.0c00368. PMID   33232156. S2CID   227167991.
  27. ↑ Waghwani HK, Douglas, T (March 2021). "Cytochrome C with peroxidase-like activity encapsulated inside the small DPS protein nanocage". Journal of Materials Chemistry B. 9 (14): 3168–3179. doi: 10.1039/d1tb00234a . PMID   33885621.
  28. ↑ "Integral Molecular" (PDF). Archived from the original (PDF) on 2009-07-31. Retrieved 2010-04-30.
  29. ↑ Willis S, Davidoff C, Schilling J, Wanless A, Doranz BJ, Rucker J (July 2008). "Virus-like particles as quantitative probes of membrane protein interactions". Biochemistry. 47 (27): 6988–90. doi:10.1021/bi800540b. PMC   2741162 . PMID   18553929.
  30. ↑ Jones JW, Greene TA, Grygon CA, Doranz BJ, Brown MP (June 2008). "Cell-free assay of G-protein-coupled receptors using fluorescence polarization". Journal of Biomolecular Screening. 13 (5): 424–9. doi: 10.1177/1087057108318332 . PMID   18567842.
  31. ↑ Adolph KW, Butler PJ (November 1976). "Assembly of a spherical plant virus". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 276 (943): 113–22. Bibcode:1976RSPTB.276..113A. doi: 10.1098/rstb.1976.0102 . PMID   13422.
  32. ↑ Ding Y, Chuan YP, He L, Middelberg AP (October 2010). "Modeling the competition between aggregation and self-assembly during virus-like particle processing". Biotechnology and Bioengineering. 107 (3): 550–60. doi:10.1002/bit.22821. PMID   20521301. S2CID   24129649.
  33. ↑ Chromy LR, Pipas JM, Garcea RL (September 2003). "Chaperone-mediated in vitro assembly of Polyomavirus capsids". Proceedings of the National Academy of Sciences of the United States of America. 100 (18): 10477–82. Bibcode:2003PNAS..10010477C. doi: 10.1073/pnas.1832245100 . PMC   193586 . PMID   12928495.
  34. ↑ Wetzel D, Rolf T, Suckow M, Kranz A, Barbian A, Chan JA, et al. (February 2018). "Establishment of a yeast-based VLP platform for antigen presentation". Microbial Cell Factories. 17 (1): 17. doi: 10.1186/s12934-018-0868-0 . PMC   5798182 . PMID   29402276.
  35. ↑ Jegerlehner A, Tissot A, Lechner F, Sebbel P, Erdmann I, Kündig T, et al. (August 2002). "A molecular assembly system that renders antigens of choice highly repetitive for induction of protective B cell responses". Vaccine. 20 (25–26): 3104–12. doi:10.1016/S0264-410X(02)00266-9. PMID   12163261.
  36. ↑ Patel KG, Swartz JR (March 2011). "Surface functionalization of virus-like particles by direct conjugation using azide-alkyne click chemistry". Bioconjugate Chemistry. 22 (3): 376–87. doi:10.1021/bc100367u. PMC   5437849 . PMID   21355575.
  37. ↑ Brune KD, Leneghan DB, Brian IJ, Ishizuka AS, Bachmann MF, Draper SJ, et al. (January 2016). "Plug-and-Display: decoration of Virus-Like Particles via isopeptide bonds for modular immunization". Scientific Reports. 6: 19234. Bibcode:2016NatSR...619234B. doi:10.1038/srep19234. PMC   4725971 . PMID   26781591.
  38. 1 2 Thrane S, Janitzek CM, Matondo S, Resende M, Gustavsson T, de Jongh WA, et al. (April 2016). "Bacterial superglue enables easy development of efficient virus-like particle based vaccines". Journal of Nanobiotechnology. 14 (1): 30. doi: 10.1186/s12951-016-0181-1 . PMC   4847360 . PMID   27117585.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.