Peptide vaccines
A technology of polypeptide antigens and amino acids, applied in the field of polypeptides and vaccines
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example 1
[0587] Example 1 HLA epitope binding prediction method and verification
[0588] Prediction of binding between specific HLAs and epitopes (9mer peptides) was based on the ImmunoEpitope Database tool for epitope prediction (www.iedb.org).
[0589] The HLA I epitope binding prediction process was validated by comparison with HLA I epitope pairs determined by laboratory experiments. Datasets of HLA I epitope pairs reported in peer-reviewed publications or public immunology databases were compiled.
[0590] The rate of agreement with the experimentally determined data set (Table 2) was determined. Binding HLA I epitope pairs for the dataset were correctly predicted with 93% probability. Coincidentally, non-binding HLA I epitope pairs were also predicted correctly with a probability of 93%.
[0591] Table 2 Analytical specificity and sensitivity of HLA epitope binding prediction methods
[0592]
[0593] The accuracy of predicting multiple HLA binding epitopes was also det...
example 2
[0597] Example 2 Epitope Presentation of Multiple HLAs Predicts Cytotoxic T Lymphocyte (CTL) Response
[0598] This study investigated whether an individual's presentation of one or more epitopes of a polypeptide antigen by one or more HLA class I molecules is predictive of a CTL response.
[0599] The study was performed by a retrospective analysis of 6 clinical trials conducted in 71 cancer patients and 9 HIV-infected patients (Table 4)1-7. Patients from these studies were treated with HPV vaccines, three different NY-ESO-1-specific cancer vaccines, an HIV-1 vaccine, and a CTLA-4-specific monoclonal antibody (ipilimmab), the Antibodies shown to reactivate CTLs against NY-ESO-1 antigen in melanoma patients. All of these clinical trials measure antigen-specific CD8+ CTL responses (immunogenicity) in study subjects after vaccination. In some cases, a correlation between CTL response and clinical response was reported.
[0600] No patients were excluded from the retrospecti...
example 3
[0612] Example 3 Retrospective Validation of ≥1 PEPI3+ Threshold as a New Biomarker for PEPI Test
[0613] In a retrospective analysis, a test cohort of 81 datasets from 51 patients was used to validate a ≥1 PEPI3+ threshold to predict antigen-specific CD8+ T cell or CTL responses. For each data set in the test cohort, it was determined whether a > 1 PEPI3+ threshold (at least one antigen-derived epitope presented by at least three class I HLAs of the individual) was met. This was compared to experimentally measured CD8+ T cell responses (CTL responses) reported in clinical trials (Table 7).
[0614] A retrospective validation demonstrated that the PEPI3+ peptide induces a CD8+ T cell response (CTL response) in an individual with a probability of 84%. 84% is the same value as determined in the analytical validation of the PEPI3+ prediction that the epitope is bound to at least 3 HLAs of the individual (Table 3). These data provide strong evidence that PEPI induces an immun...
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