Bioinformatic processes for determination of peptide binding

A process of identifying peptides in one or more proteins of interest of an infectious agent that bind to an MHC binding region and producing a vaccine comprising:

• a) obtaining amino acid sequences for an infectious agent;
• b) providing peptide binding prediction equations for multiple MHC binding regions derived by:
• (i) assembling experimentally derived data comprising a multiplicity of measurements of amino acid physicochemical properties;
• (ii) producing a correlation matrix of the experimentally derived data;
• (iii) deriving multiple uncorrelated dimensionless, weighted and ranked proxy descriptors to describe at least 80% of the variance in said physicochemical properties of individual amino acids,
• (iv) using said proxy descriptors to describe individual amino acids in peptides with known binding affinities thereby creating vectors which describe said peptides with known binding affinities, and
• (v) via neural network modeling, deriving said binding prediction equations by comparing said vectors with said known binding affinities of said peptides;
• (c) in-putting said amino acid sequences from said infectious agent protein into a computer;
• (d) identifying peptides of interest in said infectious agent protein, wherein the peptides of interest are predicted epitopes, and determining the binding affinity of the peptides of interest by applying the MHC binding prediction equations;
• (e) generating in silico at least 1000 variants of the peptides of interest by substituting individual amino acids of the peptides with a different amino acid;
• (f) applying proxy descriptors derived from the analysis of step (b) to describe each of the variant peptides generated in step (e) and applying the MHC binding prediction equations of step (b) to each of the variant peptides to determine the predicted MHC binding of each variant peptide;
• (g) comparing the predicted binding to an MHC binding region of each of the variant peptides generated in step (e) with the binding affinity of the peptides of interest in the infectious agent protein to identify variant peptide sequences with higher or lower predicted binding affinity to said MHC binding region;
• (h) synthesizing one or more of said variant peptide sequences or a nucleic acid encoding the variant peptide sequences which are identified as having a higher or lower predicted binding affinity to said MHC binding region;
• (i) formulating the synthesized peptides or a nucleic acid encoding the variant peptide sequences with a pharmaceutical carrier to provide a vaccine, and
• (j) administering the vaccine to a subject at risk of infection under conditions such that an immune response is generated.