A novel approach to design chimeric multi epitope vaccine against Leishmania exploiting infected host cell proteome.

Leishmaniasis is a major infectious disease having high mortality which could be attributed to lack of a suitable vaccine candidate. We propose a novel approach to design multiepitope vaccine to leishmaniasis exploiting specific membrane proteome from infected macrophage from host. The MHC-I, MHC-II and BC epitopes predicted for unique proteins from the infected macrophages and Leishmania and a MEV designed in various combinations (1a-1m). The epitope arrangements 1a, 1k, 1l, and 1 m showed a strong antigenicity profile and immune response. The molecular dynamics simulation indicate the 1k, 1l, and 1 m constructs have strong affinity toward TLR-2, TLR-3, and TLR-4. Overall the structural and immunogenicity profile suggests 1k is top candidate. Further, a computational model system with TLR-2, TLR-3, TLR-4, BCR, MHC-I and MHC-II was generated for 1k construct to understand the MEV interactions with immune components. Dihedral distribution and distance was enumerated to understand the movement of immune components towards 1k. The results indicate 1k has strong affinity for the immune response molecules especially TLR-3, BCR and MHC-II are coming in close contact with the MEV through the simulation. The study suggests that designed multi-epitope vaccine 1k has potential to induce proper immune response but warrants further studies.

Design and evaluation of a multiepitope vaccine for pancreatic cancer using immune-dominant epitopes derived from the signature proteome in expression datasets.

Pancreatic cancer is a highly aggressive and often lethal malignancy with limited treatment options. Its late-stage diagnosis and resistance to conventional therapies make it a significant challenge in oncology. Immunotherapy, particularly cancer vaccines, has emerged as a promising avenue for treating pancreatic cancer. Multi-epitope vaccines, designed to target multiple epitopes derived from various antigens associated with pancreatic cancer, have gained attention as potential candidates for improving therapeutic outcomes. In this study, we have explored transcriptomics and protein expression databases to identify potential upregulated proteins in pancreatic cancer cells. After examining a total of 21,054 proteins from various databases, it was discovered that 143 proteins expressed differently in malignant and healthy cells. The CTL, HTL and BCE epitopes were predicted for the shortlisted proteins. 51,840 vaccine constructs were created by concatenating CTL, HTL, and B-cell epitopes in the respective sequences. The best 86 structures were selected from a set of 51,840 designs after they were analyzed for vaxijenicity, allergenicity, toxicity, and antigenicity scores. In further simulation of the immune response using constructs, it was found that 41417, 37961, and 40841 constructs could produce a strong immune response when injected. Further, it was found that construct 37961 showed stronger interaction and stability with TLR-9 as determined from the large-scale molecular dynamics simulations. Moreover, the 37961 construct has shown interactions with TLR-9 suggests its potential in inducing immune response. In addition, construct 37961 has shown 100% predicted solubility in the E. coli expression system. Overall, the study indicates the designed construct 37961 has the potential to induce an anti-tumor immune response and long-standing protection pending further studies.