Methods to generate vaccine compositions that prime human leukocyte antigen class i restricted cd8 t-cell responses against viral non-virion-integral derived epitopes

A method to generate a vaccine composition for use against a viral pathogen, comprising:

• a. identifying non-virion-integral proteins derived Human Leukocyte Antigen class I restricted epitopes (non-VIP-derived HLAI-HRE) from the viral pathogen against which the vaccine composition is desired using standardized donor vectors for HLA and antigen ORF constructs that are paired with genomic receiver sites within functionally engineered immortal cell lines that represent programmable eAPCs that are then screened by mass spectrometry (MS) based methodologies to identify HLA-restricted antigens from integrated ORFs within the background of the intrinsic HLAI restricted repertoire derived from the eAPC proteins themselves and enables systematic analysis of the ORFs in single HLA backgrounds (monoalleleic),
• b. classifying immunogenicity of the identified non-VIP-derived HLAI-HRE in naïve CD8 T-cell populations isolated from donors without prior target virus infection, and/or in memory CD8 T-cell populations from donors with confirmed active, latent or resolved target virus infection,
• c. selecting non-VIP-derived HLAI-HRE with confirmed immunogenicity in naïve donors, or with observed CD8 T-cell responses in donors with confirmed active, latent or resolved target virus infection, and
• d. providing the selected non-VIP-derived HLAI-HRE in the vaccine composition, wherein the viral pathogen is SARS-CoV-2.