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Opisthorchis viverrini is the etiological agent of the disease opisthorchiasis and related cholangiocarcinoma (CCA). It infects fish-eating mammals and more than 10 million people in Southeast Asia suffered from opisthorchiasis with a high fatality rate. The only effective drug against this parasite is Praziquantel, which has significant side effects. Due to the lack of appropriate treatment options and the high death rate, there is a dire need to develop novel therapies against this pathogen. In this study, we designed a multi-epitope chimeric vaccine design against O. viverrini by using immunoinformatics approaches. Non-allergenic and immunogenic MHC-1, MHC-2, and B cell epitopes of three candidate proteins thioredoxin peroxidase (Ov-TPx-1), cathepsin F1 (Ov-CF-1) and calreticulin (Ov-CALR) of O. viverrini, were predicted to construct a potent multiepitope vaccine. The coverage of the HLA-alleles of these selected epitopes was determined globally. Four vaccine constructs made by different adjuvants and linkers were evaluated in the context of their physicochemical properties, antigenicity, and allergenicity. Protein-protein docking and MD simulation found that vaccines 3 was more stable and had a higher binding affinity for TLR2 and TLR4 immune receptors. In-silico restriction cloning of vaccine model led to the formation of plasmid constructs for expression in a suitable host. Finally, the immune simulation showed strong immunological reactions to the engineered vaccine. These findings suggest that the final vaccine construct has the potential to be validated by in vivo and in vitro experiments to confirm its efficacy against the CCA causing O. viverrini. more...

Primary Amoebic Meningoencephalitis (PAM), a severe lethal brain disease, is caused by a parasite, Naegleria fowleri, also known as the “brain-eating amoeba”. The chances of a patient’s recovery after being affected by this parasite are very low. Only 5% of people are known to survive this life-threatening infection. Despite the fact that N. fowleri causes a severe, fatal infection, there is no proper treatment available to prevent or cure it. In this context, it is necessary to formulate a potential vaccine that could be able to combat N. fowleri infection. The current study aimed at developing a multi-epitope subunit vaccine against N. fowleri by utilizing immunoinformatics techniques and reverse vaccinology approaches. The T- and B-cell epitopes were predicted by various tools. In order to choose epitopes with the ability to trigger both T- and B-cell-mediated immune responses, the epitopes were put through a screening pipeline including toxicity, antigenicity, cytokine-inductivity, and allergenicity analysis. Three vaccine constructs were designed from the generated epitopes linked with linkers and adjuvants. The modeled vaccines were docked with the immune receptors, where vaccine-1 showed the highest binding affinity. Binding affinity and stability of the docked complex were confirmed through normal mode analysis and molecular dynamic simulations. Immune simulations developed the immune profile, and in silico cloning affirmed the expression probability of the vaccine construct in Escherichia coli (E. coli) strain K12. This study demonstrates an innovative preventative strategy for the brain-eating amoeba by developing a potential vaccine through immunoinformatics and reverse vaccinology approaches. This study has great preventive potential for Primary Amoebic Meningoencephalitis, and further research is required to assess the efficacy of the designed vaccine. more...

The management of infectious diseases has become more critical due to the development of novel pathogenic strains with enhanced resistance. Prevotella melaninogenica, a gram-negative bacterium, was found to be involved in various infections of the respiratory tract, aerodigestive tract, and gastrointestinal tract. The need to explore novel drug and vaccine targets against this pathogen was triggered by the emergence of antimicrobial resistance against reported antibiotics to combat P. melaninogenica infections. The study involves core genes acquired from 14 complete P. melaninogenica strain genome sequences, where promiscuous drug and vaccine candidates were explored by state-of-the-art subtractive proteomics and reverse vaccinology approaches. A stringent bioinformatics analysis enlisted 18 targets as novel, essential, and non-homologous to humans and having druggability potential. Moreover, the extracellular and outer membrane proteins were subjected to antigenicity, allergenicity, and physicochemical analysis for the identification of the candidate proteins to design multi-epitope vaccines. Two candidate proteins (ADK95685.1 and ADK97014.1) were selected as the best target for the designing of a vaccine construct. Lead B- and T-cell overlapped epitopes were joined to generate potential chimeric vaccine constructs in combination with adjuvants and linkers. Finally, a prioritized vaccine construct was found to have stable interactions with the human immune cell receptors as confirmed by molecular docking and MD simulation studies. The vaccine construct was found to have cloning and expression ability in the bacterial cloning system. Immune simulation ensured the elicitation of significant immune responses against the designed vaccine. In conclusion, our study reported novel drug and vaccine targets and designed a multi-epitope vaccine against the P. melaninogenica infection. Further experimental validation will help open new avenues in the treatment of this multi-drug-resistant pathogen. more...