Visceral leishmaniasis (VL) is a vector-borne neglected tropical protozoan disease with high fatality and no certified vaccine. Conventional vaccine preparation is challenging and tedious. Here in this work, we created a global multiepitope subunit vaccination against VL utilizing innovative immunoinformatics technique based on the extensively conserved epitopic regions of the PrimPol protein of Leishmania donovani consisting of four subunits which were analyzed and studied, out of which DNA primase large subunit and DNA polymerase α subunit B were evaluated as antigens by Vaxijen 2.0. The multiepitope vaccine design includes a single adjuvant β-defensins, eight CTL epitopes, eight HTL epitopes, seven linear BCL epitopes and one discontinuous BCL epitope to induce innate, cellular and humoral immune responses against VL. The Expasy ProtParam tool characterized the physiochemical parameters of the vaccine. At the same time, SOLpro evaluated our vaccine constructs to be soluble upon expression. We also modeled the stable tertiary structure of our vaccine construct through Robetta modeling for molecular docking studies with toll-like receptor proteins through HADDOCK 2.4. Simulations based on molecular dynamics revealed an intact vaccine and TLR8 complex, supporting our vaccine design's immunogenicity. Also, the immune simulation of our vaccine by the C-ImmSim server demonstrated the potency of the multiepitope vaccine construct to induce proper immune response for host defense. Codon optimization and in silico cloning of our vaccine further assured high expression. The outcomes of our study on multiepitope vaccine design significantly produced a potential candidate against VL and can potentially eradicate the disease in the future after clinical investigations.Communicated by Ramaswamy H. Sarma.

2024-12-09·Journal of Biomolecular Structure and Dynamics

Reverse vaccinology & immunoinformatics approach to design a multiepitope vaccine (CV3Ag-antiMRSA) against methicillin resistant Staphylococcus aureus (MRSA) – a pathogen affecting both human and animal health

Article

作者: Bandopadhyay, Satarupa ; Pais, Roshan ; Das Mitra, Susweta ; Karunakar, Prashantha ; Rajegowda, Sushmitha ; Kumar, Bharat

Infections caused by drug resistant bacteria is a silent detrimental pandemic affecting the global health care profoundly. Methicillin resistant Staphylococcus aureus (MRSA) is a pathogen that causes serious infections in different settings (community, hospital & veterinary) whose treatment remains highly challenging due to its powerful characteristics (antibiotic resistance strategies, virulence factors). In this study, we used reverse vaccinology (RV) approach and designed an immunogenic multi epitope vaccine (CV3Ag-antiMRSA) targeting three potential antigen candidates viz., mecA encoding transpeptidase (PBP2a) protein responsible for conferring methicillin resistance and two virulence determinants - hlgA encoding gamma-hemolysin component A (a pore forming toxin) and isdB encoding iron regulated surface determinant B (heme transport component that allows S. aureus to scavenge iron from host hemoglobin and myoglobin). We employed an array of immunoinformatic tools/server to identify and use immunogenic epitopes (B cell and MHC class) to develop the chimeric subunit vaccine V4 (CV3Ag-antiMRSA) with immune modulating adjuvant and linkers. Based on different parameters, the vaccine construct V4 (CV3Ag-antiMRSA) was determined to be suitable vaccine (antigenic and non-allergen). Molecular docking and simulation of CV3Ag-antiMRSA with Toll Like Receptor (TLR2) predicted its immuno-stimulating potential. Finally, in silico cloning of CV3Ag-antiMRSA construct into pet28a and pet30 vector displayed its feasibility for the heterologous expression in the E. coli expression system. This vaccine candidate (CV3Ag-antiMRSA) designed based on the MRSA genomes obtained from both animal and human hosts can be experimentally validated and thereby contribute to vaccine development to impart protection to both animal and human health.Communicated by Ramaswamy H. Sarma.

2024-12-01·International Immunopharmacology

Rational computational design and development of an immunogenic multiepitope vaccine incorporating transmembrane proteins of Staphylococcus lugdunensis

Article

作者: Alsanie, Walaa F ; Alsanie, Walaa F. ; Alamri, Abdulhakeem S. ; Khan, Aswad ; Alhomrani, Majid ; Iftikhar, Muhammad Azeem ; Aziz, Tariq ; Majeed, Muhammad Nouman ; Naveed, Muhammad ; Fatima, Furrmein ; Alamri, Abdulhakeem S ; Rehman, Hafiz Muzzammel ; Javed, Tayyab

Staphylococcus lugdunensis has emerged as a significant human pathogen, responsible for a range of infections from skin and soft tissue infections to endocarditis and bacteremia. Notably, abscess formation is a common manifestation, reflecting its potential shift from a benign skin commensal to a serious pathogen, akin to infective endocarditis. With the rising prevalence of antibiotic resistance, there is a pressing need for novel therapeutic strategies. This study addresses this need by exploring the development of an effective S. lugdunensis vaccine. Multiepitope vaccines, which incorporate various antigenic fragments from S. lugdunensis proteins, offer a promising approach to elicit a robust immune response. Computational tools are instrumental in selecting epitopes based on their predicted immunogenicity and non-toxicity. Molecular docking and molecular dynamics (MD) simulations further elucidate the interactions between vaccine constructs and immune system molecules, such as B-cell and T-cell receptors, providing detailed insights into binding affinity, specificity, and stability. This study highlights the potential of integrating multiepitope vaccine design with advanced computational methods to expedite and enhance vaccine development, addressing a critical gap amid escalating antibiotic resistance.

100 项与 Multiepitope vaccines(Pontifical Catholic University of Rio de Janeiro) 相关的药物交易

登录后查看更多信息