Immunogenicity comparison of neoantigen vaccines through different delivery platform

Abstract

Abstract Neoantigens are promising cancer vaccine candidates because they’re cancer-specific and can be predicted from the patient’s genomic data. A major challenge for developing potent neoantigen vaccines is the low immunogenicity of neoepitopes. DNA vaccines can deliver multiple epitopes and cytokines as an adjuvant in a single plasmid, and its immunogenicity can be further enhanced through heterologous prime-boost strategy. Here, we hypothesized utilizing DNA prime, adenovirus boost (refer to the DDA approach) strategy can improve the immunogenicity of neoantigen vaccines. To investigate whether vaccination through the DDA approach or DDA combine GM-CSF as adjuvant can improve the immunogenicity of neoantigen vaccines. Using IEDB analysis resource to predict and rank the top 21 MHC class I epitopes (short peptide) for the B16F10 tumor while 27mer peptides (long peptide) were synthesized to cover both MHC class I and class II epitopes. The 27mer neoantigen sequences of the selected 21 MHC class I epitopes were cloned into one plasmid and adenoviral vector with or without GM-CSF sequence linked by p2a. Mice were immunized through the DDA approach or peptides with polyI:C. In the peptide vaccine, the majority of the response were mediated by CD4+ T cells, only one peptide can induce CD8+ T cells response. For the DDA approach, 14% epitopes can induce CD8+ T cell response in mice immunized with DNA vaccine. Moreover, in the group with genetic encoded GM-CSF. it has significantly enhanced CD8+T cell response compare to the former, which dramatically improved the immunogenicity of neoantigen vaccines. Our preliminary data also showed that immunization of DNA vaccines significantly delayed tumor growth.