School Of Basic And Applied Sciences

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    Cloning, expression and in vitro validation of chimeric multi epitope vaccine candidate against visceral leishmaniasis infection
    (Elsevier Inc., 2023-04-11T00:00:00) Ojha, Rupal; Chand, Kailash; Vellingiri, Balachandar; Prajapati, Vijay Kumar
    Visceral Leishmaniasis or Kala-Azar is one of the most severe and deadly neglected tropical disease caused by the Leishmania parasite. A few number of vaccines are going through different phases in clinical trial but failing of these vaccines in successive phase trial or less efficacy, urge to develop highly immunogenic and cost-effective treatment to get rid of deadly VL. This study focuses on the development of more potent vaccine candidate against VL. The recombinant vaccine candidate LeiSp was expressed in Pichia pastoris, followed by purification and characterization. The purified protein was also tested for any post-translation modification, which favors being a potent immunogenic candidate. Further, the expression modulation of different pro-inflammatory and anti-inflammatory cytokines was evaluated in THP1 cell lines. A significant upregulation in the expression of pro-inflammatory cytokines while no significant changes were observed in the expression of anti-inflammatory cytokines. The impact of recombinant vaccine protein candidates in infected conditions were determined. Here, upon treatment with chimeric vaccine protein candidate, we observed a considerable recovery in the expression level of pro-inflammatory cytokines, which were downregulated upon infection alone. In addition to this, we found a significant decrease in the expression of anti-inflammatory cytokines, which were upregulated during infection alone. We further validated our findings in infected hPBMCs and observed similar expression modulation of pro-inflammatory and anti-inflammatory cytokines with and without treatment. Thus, the present study indicates that the chimeric LeiSp protein which was designed using bioinformatics approaches shows a potential inductive efficacy for pro-inflammatory cytokines in Leishmania-infected cells. � 2023 Elsevier Inc.
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    Fractional time-delay mathematical modeling of Oncolytic Virotherapy
    (Elsevier Ltd, 2021-06-19T00:00:00) Kumar, Pushpendra; Erturk, Vedat Suat; Yusuf, Abdullahi; Kumar, Sunil
    An emerging treatment tool which uses replication-competent viruses to dissipate cancers without causing deficit to normal tissues, named as oncolytic virotherapy, is discussed in the article. We analysed a fractional delay dynamical model on the oncolytic virotherapy compositing viral lytic cycle and virus-specific cytotoxic T lymphocyte (CTL) response. We used a well known Caputo fractional derivative to analyse the structure of the given dynamical model. Using the literature of fixed-point theory, the given time-delay model is specified to have existence of a unique solution. We established different types of graphical simulations for the various values of R0 and R1. We observed a different behaviour of the given fractional model as compare to the integer order model. The given algorithm is smooth in use and reliable to apply on different delay dynamical models. � 2021 Elsevier Ltd
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    Multi-pathogen based chimeric vaccine to fight against COVID-19 and concomitant coinfections
    (Springer Science and Business Media B.V., 2023-05-06T00:00:00) Ojha, Rupal; Singh, Satyendra; Gupta, Nidhi; Kumar, Ketan; Padhi, Aditya K.; Prajapati, Vijay Kumar
    Background: COVID-19 has proved to be a fatal disease of the year 2020, due to which thousands of people globally have lost their lives, and still, the infection cases are at a high rate. Experimental studies suggested that SARS-CoV-2 interacts with various microorganisms, and this coinfection is accountable for the augmentation of infection severity. Methods and results: In this study, we have designed a multi-pathogen vaccine by involving the immunogenic proteins from S. pneumonia, H. influenza, and M. tuberculosis, as they are dominantly associated with SARS-CoV-2. A total of 8 antigenic protein sequences were selected to predict B-cell, HTL, and CTL epitopes restricted to the most prevalent HLA alleles. The selected epitopes were antigenic, non-allergenic, and non-toxic and were linked with adjuvant and linkers to make the vaccine protein more immunogenic, stable, and flexible. The tertiary structure, Ramachandran plot, and discontinuous B-cell epitopes were predicted. Docking and MD simulation study has shown efficient binding of the chimeric vaccine with the TLR4 receptor. Conclusion: The in silico immune simulation analysis has shown a high level of cytokines and IgG after a three-dose injection. Hence, this strategy could be a better way to decrease the disease's severity and could be used as a weapon to prevent this pandemic. � 2023, The Author(s), under exclusive licence to Springer Nature B.V.