Poorer countries, which do not have the funds to produce large amounts of vaccines, could benefit from VLP technology. Fighting viruses with their own weapons is not an entirely new approach. A simple and successful tool, however, has only been discovered recently: virus-like particles VLPs resemble and mimic the structure of authentic viruses without being infectious. As they do not contain any viral genetic material, they have significant potential to elicit a strong immune response, without doing any actual harm. Most vaccines are still produced in fertilised chicken eggs — a complex process that has been in use for around 80 years and takes at least six months.
While this older technology, developed by the US Centers for Disease Control, still works for some areas, it is not nearly fast enough to address emerging seasonal or pandemic viral strains. Despite this, some areas of the industry are still tentative towards VLPs and would rather invest in more traditional ways of drug development methods.
Only the highly pressured vaccine market has welcomed the approach with open arms, allowing pharmaceutical companies to produce large amounts of a cost-effective vaccine within tight timeframes, bringing the timeline of development down to only a few months. Next-gen vaccines One company that jumped on the bandwagon, specialising in VLP-based vaccines since , is Canadian biotechnology firm Medicago.
According to its vice-president of business development, Frederic Ors, the next generation of vaccines will be developed with this technique. The main difference is that their core genetic material is non-infectious, making them unable to replicate. In addition, VLP-based vaccines have been shown to provide protection against different strains of a virus other than those for which the vaccine was formulated.
Robert J Geraghty, associate professor and director of the Center for Drug Design at the University of Minnesota in the US, sees the biggest benefits for VLPs in their safety: "When compared to attenuated vaccines and in the presence of more complex epitopes [the parts of an antigen molecule to which an antibody attaches itself] they provide a wider immune response when compared to a single subunit vaccine," he says.
Healthy tobacco VLPs are traditionally produced from virus families or from mammalian cell lines.
Virus like particle-based vaccines against emerging infectious disease viruses
Medicago has however concentrated on the production of the particles from plants cell lines, using the Australian tobacco strain Nicotiana benthamiana. To produce the particles from the tobacco plant, the company synthesises the DNA sequence of the latest flu strain. Proper folding that allows the formation of specific structures is essential for the function of VLPs in clinical use. Various in vitro analytical methods, in conjunction with in vivo evaluation, have been established to monitor the presence of native-like epitopes on VLPs obtained from E.
This review highlights examples of E. As a robust protein expression host, E. In vaccine development, high product cost would restrict utilization, especially in developing countries.
There is thus an urgent need for new vaccine manufacturing platforms that are able to rapidly and cheaply produce vaccine antigens. Platform technology based on E. The high yield of capsid proteins or structural proteins the basic unit of VLPs could significantly reduce the time and the cost of vaccine production. Several E.
Targeted Drug Delivery and Vaccinology Approaches Using Virus-like Particles for Cancer
Hecolin, a p VLP-based vaccine, containing aa of open reading frame 2 of a genotype 1 strain of HEV, 25 was the first commercialized E. In addition, VLPs have been utilized as vaccine platforms to increase the immunogenicity of antigens. These chimeric VLP vaccines were both targeted against infectious and non-infectious diseases. The high-cost of the vaccines was the main limitation preventing worldwide implementation.
The HEV, the causative agent of hepatitis E, is the sole member of the genus Hepevirus within the family Hepeviridae and transmits primarily in a fecal-oral manner. Mammalian HEV is classified into four major genotypes, but only one serotype. HEV is a nm, non-enveloped, positive-sense single-stranded RNA icosahedral virus with an approximately 7.
Hecolin, the first prophylactic hepatitis E vaccine, was licensed in and launched in in China. The comparable p VLPs characteristics of the antigen produced at different scales indicated that the antigen manufacturing process was robust and scalable.
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Multi-year stability is required for marketed vaccines. The results demonstrated overall high structural stability of p VLPs over 24 months.
Analytical toolbox for the characterization of VLPs. These vaccines are generally well tolerated. Xiamen Innovax Biotech has used E. L1 is the HPV major structural protein the other minor capsid protein is L2. VLPs have been used as a vaccine delivery platform to increase the immunogenicity of antigens. Malaria, caused by the Plasmodium parasite, is a serious public health problem in the tropics. The results of a phase I trial showed clinical efficiency against malaria parasites.
Due to viral drifts and shifts, a particular influenza vaccine cannot provide long-term immunity. The immunogenicity has been confirmed in a phase I clinical trial NCT A phase I trial has demonstrated that gH1-Qbeta was able to induce high titer of anti-viral antibodies with a favorable safety profile.
In addition, many E. The potency of these E. The efficacy and safety of a vaccine need to be demonstrated for licensing in human use. Structural and functional assessment of VLPs is the most critical antigen characterization assays for recombinant protein based vaccines.
The spatial or higher-order structure of the vaccine antigen is the basis of the various biological functions of protein-based vaccines. Quantitative analysis of the functional epitopes on VLPs using monoclonal antibody-based assays can be an advantageous way to ensure vaccine safety and efficacy. The identification of the primary structure indicated that the target protein composed of VLPs was successfully expressed. Biochemical characterization includes the primary amino acid sequence, molecular weight, isoelectric point, and purity of the VLPs.
SDS-PAGE, the most common method that used to determine the purity, integrity and molecular weight of the purified antigen. Neutralizing and immunodominant epitopes on antigen are the structural basis of an epitope to elicit functional and protective antibodies. VLPs have been widely used in vaccinology. The next generation of VLP-based vaccine candidates must be creative in form and function to satisfy diverse needs.
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Re-engineering or grafting epitopes in chimeric VLPs may widen the coverage spectrum compared to monovalent vaccines. The commercial VLP-based vaccines have been constructed through eukaryotic or prokaryotic systems. As a manufacturing platform, E. Their limitation factors included: 1 lack of ability to produce the correct disulfide bonds, 2 fail to produce recombinant proteins with mammalian-like post-translational modifications, 3 the problems of protein solubility, and 4 the presence of endotoxins lipopolysaccharide, LPS.
Currently, numerous mutant E. Zhao et al. Most gram-negative bacteria contain endotoxins, LPSs, which can induce a pyrogenic response. However, the removal of LPSs increases the complexity and the cost of protein purification processes. In summary, several promising E. The success of E. VLPs mimicking viral capsids or chimeric VLPs by grafting epitopes of interests to a well-behaved VLP display vector are platforms for future vaccines via structure-based modular design.
Different analytical methods for antigen characterization provide important supports for recombinant VLP-based vaccines to ensure their efficacy and safety, and most importantly the preservation of native-like epitopes during manufacturing, storage and transportation of the vaccines. Further improvements on the E.
Better understanding of protein production and self-assembly would facilitate scale up and better process control at commercial production scale. As a result, rapid and inexpensive VLP-based vaccine production could be realized for global accessibility. Zepp, F.