Immunotherapies are a promising treatment option especially for the management of TNBC owing to its higher levels of tumour-associated antigens together with higher mutational load. Of note, the administration of preventive vaccines in the early stage of the cancer holds promise for effective disease management. Therefore, the present study aimed to develop a novel multi-epitope peptide-based vaccination against TNBC employing SOX9, which has recently been recognized as a key regulator of TNBC metastasis. The immunodominant regions from the SOX9 protein were computed and assessed based on their ability to elicit both T and B lymphocyte mediated responses. The resultant epitopes were fused using appropriate linkers (EAAAK, KK, AAY and GPGPG) and adjuvant (50S ribosomal protein L7/L12) to enhance the vaccine’s immunogenicity. The physicochemical properties and population coverage were also anticipated for the constructed vaccine. Adding together, docking and dynamics simulation studies were performed on the modelled vaccine against TLR-4 to provide insight into the stability. Finally, the designed vaccine was cloned into the pET28 (+) vector and immunological simulation studies were carried out. These results demonstrate that our designed vaccine had the potency to trigger humoral and cellular immune responses. Based on these collective evidences, the final proposed vaccine could be an interesting therapeutics for the management of TNBC in the near future. Graphical abstract Schematic representation of an efficient vaccine design framework by combining the range of immunoinformatics strategies. Supplementary Information The online version contains supplementary material available at 10.1007/s11030-022-10539-w.

The Human Betaherpesviruses HHV-5 and HHV-6 are quite inimical in immunocompromised hosts individually. A co-infection of both has been surmised to be far more disastrous. This can be attributed to a synergetic effect of their combined pathologies. While there have been attempts to develop a vaccine against each virus, no efforts were made to contrive an effective prophylaxis for the highly detrimental co-infection. In this study, an ensemble of viral envelope glycoproteins from both the viruses was utilized to design a multi-epitope vaccine using immunoinformatics tools. A collection of bacterial protein toll-like receptor agonists (BPTAs) was screened to identify a highly immunogenic adjuvant for the vaccine construct. The constructed vaccine was analysed using an array of methodologies ranging from World population coverage analysis to Immune simulation, whose results indicate high vaccine efficacy and stability. Furthermore, codon optimization and in silico cloning analysis were performed to check for efficient expression in a bacterial system. Collectively, these findings demonstrate the potential of the constructed vaccine to elicit an immune response against HHV-5 and HHV-6, thus supporting the viability of in vitro and in vivo studies.

Immunotherapy is emerging as a potential therapeutic strategy for triple negative breast cancer (TNBC) owing to the immunogenic landscape of its tumor microenvironment. Interestingly, peptide-based cancer vaccines have garnered a lot of attention as one of the most promising cancer immunotherapy regimens. Thus, the present study intended to design a novel, efficacious peptide-based vaccine against TNBC targeting myeloid zinc finger 1 (MZF1), a transcription factor that has been described as an oncogenic inducer of TNBC metastasis. Initially, the antigenic peptides from MZF1 were identified and evaluated based on their likelihood to induce immunological responses. The promiscuous epitopes were then combined using a suitable adjuvant (50S ribosomal L7/L12 protein) and linkers (AAY, GPGPG, KK, and EAAAK) to reduce junctional immunogenicity. Furthermore, docking and dynamics analyses against TLR-4 and TLR-9 were carried out to understand more about their structural stability and integrity. Finally, the constructed vaccine was subjected to in silico cloning and immune simulation studies. Overall, the findings imply that the designed chimeric vaccine could induce strong humoral and cellular immune responses in the desired organism. In light of these findings, the final multi-epitope vaccine could be used as an effective prophylactic treatment for TNBC and may pave the way for future research.