Method of compact peptide vaccines using residue optimization

A method of forming an immunogenic peptide composition, the method comprising:

• using a processor to perform the steps of:
• creating a first peptide set by selecting a plurality of unmodified peptide sequences, wherein the plurality of unmodified peptide sequences is associated with a tumor neoantigen, a pathogen proteome, or a self-protein;
• determining a plurality of peptide-HLA immunogenicity metrics for each peptide sequence in the first peptide set;
• determining whether each peptide sequence in the first peptide set has a peptide-HLA immunogenicity metric that passes a threshold with respect to at least three HLA alleles;
• creating a second peptide set comprising the first peptide set and a plurality of modified peptide sequences, wherein each modified peptide sequence of the plurality of modified peptide sequences comprises a substitution of at least one amino acid residue of a peptide sequence in the first peptide set;
• determining a plurality of peptide-HLA immunogenicity metrics for each peptide sequence in the second peptide set;
• and
• creating a third peptide set by selecting a subset of the second peptide set, wherein the selecting comprises a predicted vaccine performance, wherein the computing of the predicted vaccine performance comprises excluding a peptide-HLA immunogenicity metric with respect to a first HLA allele for a modified peptide sequence if a peptide-HLA immunogenicity metric for an unmodified peptide sequence associated with the modified peptide sequence does not pass the threshold with respect to the first HLA allele, and wherein the predicted vaccine performance is a function of a peptide-HLA immunogenicity metric of each peptide sequence in the third peptide set;
• performing an experimental assay to obtain a peptide-HLA immunogenicity metric for at least one peptide sequence of the third peptide set;
• and
• forming an immunogenic peptide composition comprising the at least one peptide sequence of the third peptide set for which the experimental assay was performed.

A method of forming an immunogenic peptide composition, the method comprising:

• using a processor to perform the steps of:
• creating a first peptide set by selecting a plurality of unmodified peptide sequences, wherein each peptide sequence of the plurality of unmodified peptide sequences is associated with a tumor neoantigen, a pathogen proteome, or a self-protein;
• determining a plurality of peptide-HLA binding scores for each peptide sequence in the first peptide set;
• determining whether each peptide sequence in the first peptide set has a peptide-HLA binding score that passes a threshold with respect to at least three HLA alleles;
• creating a second peptide set comprising the first peptide set and a plurality of modified peptide sequences, wherein each modified peptide sequence of the plurality of modified peptide sequences comprises a substitution of at least one amino acid residue of a peptide sequence in the first peptide set;
• determining a plurality of peptide-HLA binding scores for each peptide sequence in the second peptide set;
• and
• creating a third peptide set by selecting a subset of the second peptide set, wherein the selecting comprises computing a predicted vaccine performance, wherein the computing of the predicted vaccine performance comprises excluding a peptide-HLA binding score with respect to a first HLA allele for a modified peptide sequence if a peptide-HLA binding score for an unmodified peptide sequence associated with the modified peptide sequence does not pass the threshold with respect to the first HLA allele, and wherein the predicted vaccine performance is a function of a peptide-HLA binding score of each peptide sequence in the third peptide set;
• performing an experimental assay to obtain a peptide-HLA immunogenicity metric for at least one peptide sequence of the third peptide set;
• and
• forming an immunogenic peptide composition comprising the at least one peptide sequence of the third peptide set for which the experimental assay was performed.

A method of forming an immunogenic peptide composition, the method comprising:

• using a processor to perform the steps of:
• creating a first peptide set by selecting a plurality of unmodified peptide sequences, wherein at least one peptide sequence of the plurality of unmodified peptide sequences is associated with a tumor neoantigen, a pathogen proteome, or a self-protein;
• determining a plurality of peptide-HLA binding scores for each peptide sequence in the first peptide set;
• determining whether each peptide sequence in the first peptide set has a peptide-HLA binding score that passes a threshold with respect to at least three HLA alleles;
• creating a second peptide set comprising the first peptide set and a plurality of modified peptide sequences, wherein each modified peptide sequence of the plurality of modified peptide sequences comprises a substitution of at least one amino acid residue of a peptide sequence in the first peptide set;
• determining a plurality of peptide-HLA binding scores for each peptide sequence in the second peptide set;
• and
• creating a third peptide set by selecting a subset of the second peptide set, wherein the selecting comprises computing a predicted vaccine performance based on an HLA type of a subject, and wherein the computing of the predicted vaccine performance comprises excluding a peptide-HLA binding score with respect to a first HLA allele for a modified peptide sequence if a peptide-HLA binding score for an unmodified peptide sequence associated with the modified peptide sequence does not pass the threshold with respect to the first HLA allele;
• performing an experimental assay to obtain a peptide-HLA immunogenicity metric for at least one peptide sequence of the third peptide set;
• and
• forming an immunogenic peptide composition comprising the at least one peptide sequence of the third peptide set for which the experimental assay was performed.