A reverse vaccinology approach to development a multi-epitope vaccine candidate against multiple myeloma: An in-silico study

Abstract Multiple myeloma (MM) is a clonal plasma cell malignancy that remains largely incurable despite recent advances in therapies. As a result, new immunotherapeutic methods are needed to selectively activate T cells that fight MM using antigens associated with MM. NSD2 is one of the main dysregulated antigens overexpressed in high-risk MM and linked to the poor prognosis. We have utilized various bioinformatics approaches to choose and develop a promising multi-epitope vaccine candidate against multiple myeloma (MM). Multi-epitope vaccine (MEV) has three critical components, two main subsets of T cells: cytotoxic T lymphocytes (CTLs), helper T lymphocytes (HTLs), and adjuvants. We focused on NSD2-derived epitopes (TepiTool) that had high antigenicity (VaxiJen), no allergenicity (AllergenFP), and the best solubility (SOLpro) to guarantee that they were safe and specific for the immune system. Subsequently, CTL and HTL epitopes were identified and incorporated into the MEV construct. The CTL epitopes are joined by AAY motifs to proteasomal processing and MHC-I presentation. HTL epitopes were also linked by GPGPG spacers to encourage CD4+ T cell help and B cell activation. The previous step was followed by adding CpG motifs through the EAAAK linker as an adjuvant (TLR9 agonist) to boost Th1-polarized CTL responses. This procedure improved dendritic cell cross-priming in MM trials. An optimized MEV was explicitly designed for MM treatment. The novel MEV platform can be used for prophylactic or therapeutic purposes because it can potentially stimulate both cellular and humoral immune responses. Although this initial information is promising, comprehensive in vitro and in vivo evaluation is required to validate it as a vaccine candidate.