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Vaccine Design - Immunological Bioinformatics

BY: Geetanjali Murari | Category: Others | Submitted: 2013-03-18 10:24:53
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Article Summary: "The bioinformatics tools can help us in designing vaccines. Usually, designing of vaccine require a time period of 5-15 years but bioinformatics can bring this timeline down to 1-2 years. This article depicts the methos of developing epitope based subunit vaccine..."

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Vaccines are the antigens that train the adaptive immune system to recognise and fight the infection without requiring exposure to the pathogen. The adaptive immune system is pathogen specific. It can be of two types, i.e., humoral and cellular.

The conventional vaccine development might take upto 5 to 15 years. First, we need to cultivate the desired microorganism, isolate the antigen and test their immunogenicity. Then putify the components to be used, clone genes and design the required vaccines. While, with the help of bioinformatics, the vaccine development might take just 1-2 years. Start from the whole genomic sequence which is already present in the biological database. Through computer predictions, in-silico vaccines are developed. Prepare DNA vaccines and express the recombinant proteins. This can result into the vaccine designing. This whole process is known as reverse vaccinology.

The epitope is the part of a macromolecule that is recognised by the immune system (T or B cells). The new subunit epitope based vaccines are being designed. These vaccines can overcome safety concerns with attenuated pathogens. They can target conserved epitopes in variable or rapidly mutating pathogens. The bioinformatics tools can be used to select the target proteins and epitopes. The strategy of epitope based vaccine design is mentioned here. The proteomic data of the pathogen is collected. The putative vaccine epitopes are identified by in-silico methods. In-vitro testing, like, Human Leukocyte Antigen (HLA) and T cell binding assays are performed. The genes of selected epitopes are cloned and expressed in the suitable vectors. The required vaccines are produced, purified and collected. The immunological testing are done in animal models both in-vivo and ex-vivo for validation of the product. Hence, the vaccine is developed and designed.

Major Histocompatibility Complex are diverse in nature. These MHC molecules differ in the peptides to which they bind. A useful vaccine must elicit a response in most of the target population. The proteins that contain many epitopes are recognised by the common MHC alleles. These are known as promiscuous binders. The HLA supertype refers to a set of HLA alleles with overlapping peptide binding specificities. The alleles in the given HLA supertype often represents the same epitope, which refer to the region on the surface of an antigen capable of eliciting an immune response for T cell recognition. There are several databases storing the MHC binding and non-binding peptides or T cell epitopes. For example, Jenpep (Database of MHC and TAP binding peptides), MHCPEP (database of MHC binding peptides), FIMM (database of functional immunology), MHCBN (database containing tools for subunit vaccine design), HLA ligand/motif (ligand database), HIV molecular immunology (HIV-1 CTL and HTL epitopes), etc. The various online tools for MHC binding peptides or T cell epitopes prediction are BIMAS, PREDEP, Epipredict, Predict, Propred, CTLPred, RANKPREP, SVMHC, MHCPred, IEDB.
The vaccine candidates should be conserved across different stages of the pathogens as well as strains. This is known as conservancy analysis. The vaccines should be promiscuous in nature, they must have binding affinity with more than one MHC allele. The epitope sets are restricted by different MHC alleles and must cover the major population. This gives the population coverage analysis.

The epitope based vaccines are potential and controllable. They can target multiple conserved epitopes in rapidly mutating pathogens. It can overcome safety concerns associated with the entire organisms or proteins. These vaccines are useful and should be designed more frequently.

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Geetanjali Murari
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