A method for individualizing the prediction of immunogenicity of protein vaccines and biologic therapeutics: individualized T cell epitope measure (iTEM).
The promise of pharmacogenomics depends on advancing predictive medicine. To address this need in the area of immunology, we developed the individualized T cell epitope measure (iTEM) tool to estimate an individual's T cell response to a protein antigen based on HLA binding predictions. In this study, we validated prospective iTEM predictions using data from in vitro and in vivo studies. We used a mathematical formula that converts DRB1* allele binding predictions generated by EpiMatrix, an epitope-mapping tool, into an allele-specific scoring system. We then demonstrated that iTEM can be used to define an HLA binding threshold above which immune response is likely and below which immune response is likely to be absent. iTEM's predictive power was strongest when the immune response is focused, such as in subunit vaccination and administration of protein therapeutics. iTEM may be a useful tool for clinical trial design and preclinical evaluation of vaccines and protein therapeutics.
Cohen
Tobias
T
EpiVax, Providence, RI 02903, USA.
Moise
Leonard
L
Ardito
Matthew
M
Martin
William
W
De Groot
Anne S
AS
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000737:chemistry / Q000276:immunology; D016009:Chi-Square Distribution; D019295:Computational Biology / Q000379:methods*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D015798:HLA-DR1 Antigen / Q000276:immunology; D059811:HLA-DRB1 Chains; D016014:Linear Models; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D011506:Proteins / Q000737:chemistry / Q000276:immunology; D015203:Reproducibility of Results; D012984:Software; D013601:T-Lymphocytes / Q000276:immunology; D022223:Vaccines, Subunit / Q000737:chemistry / Q000276:immunology*
D000941:Antigens; D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; D015789:HLA-A2 Antigen; D006684:HLA-DR Antigens; D015798:HLA-DR1 Antigen; D059811:HLA-DRB1 Chains; D011506:Proteins; D022223:Vaccines, Subunit