Reverse vaccinology approach to design a novel multi-epitope subunit vaccine against avian influenza A (H7N9) virus

Abstract

32 33 H7N9, a novel strain of avian origin influenza was the first recorded incidence where a human was 34 transited by a N9 type influenza virus. Effective vaccination against influenza A (H7N9) is a major 35 concern, since it has emerged as a life threatening viral pathogen. Here, an in silico reverse 36 vaccinology strategy was adopted to design a unique chimeric subunit vaccine against avian 37 influenza A (H7N9). Induction of humoral and cell-mediated immunity is the prime concerned 38 characteristics for a peptide vaccine candidate, hence both T cell and B cell immunity of viral 39 proteins were screened. Antigenicity testing, transmembrane topology screening, allergenicity and 40 toxicity assessment, population coverage analysis and molecular docking approach were adopted 41 to generate the most antigenic epitopes of avian influenza A (H7N9) proteome. Further, a novel 42 subunit vaccine was designed by the combination of highly immunogenic epitopes along with 43 suitable adjuvant and linkers. Physicochemical properties and secondary structure of the designed 44 vaccine were assessed to ensure its thermostability, hydrophilicity, theoretical PI and 45 structural behavior. Homology modeling, refinement and validation of the designed vaccine 46 allowed to construct a three dimensional structure of the predicted vaccine, further employed to 47 molecular docking analysis with different MHC molecules and human immune TLR8 receptor 48 present on lymphocyte cells. Moreover, disulfide engineering was employed to lessen the high 49 mobility region of the designed vaccine in order to extend its stability. Furthermore, we 50 investigated the molecular dynamic simulation of the modeled subunit vaccine and TLR8 51 complexed molecule to strengthen our prediction. Finally, the suggested vaccine was reverse 52 transcribed and adapted for E. coli strain K12 prior to insertion within pET28a(+) vector for 53 checking translational potency and microbial expression. 54 55

Comprehensive Genome Based Analysis ofVibrio parahaemolyticusfor Identifying Novel Drug and Vaccine Molecules: Subtractive Proteomics and Vaccinomics Approach

“…Although both cytoplasmic and membrane proteins serve the purpose as therapeutic targets (Michael et al, 2014), membrane proteins are best suited for vaccine candidates (Baliga et al, 2018;Hasan et al, 2019a). Hence, in this study, membrane proteins (25) were used for vaccine construction, whereas cytoplasmic proteins (16) were proposed as suitable drug targets.…”

“…Several advantages help the researchers to select membrane proteins both as drug and vaccine candidates as their functions can be easily studied through computer-based approaches than wetlab process (Hasan et al, 2019a;Hasan et al, 2019b). In this study, two vaccine targets, 'Sensor histidine protein kinase UhpB (Q87HJ8)' and 'Flagellar hook-associated protein (Q87JH9)' were selected after screening the novel outer-membrane proteins (25) based on their antigenicity score and human microbiome non-homology analysis (Table 6).…”

Conglomeration of highly antigenic nucleoproteins to inaugurate a heterosubtypic next generation vaccine candidate against Arenaviridae family

“…The allergenicity pattern of the predicted epitopes were determined through four servers i.e. AllerTOP (Dimitrov et al, 2013), AllergenFP (Dimitrov et al, 2014), Allergen Online (Goodman et al, 2016) and Allermatch (Fiers et al, 2004) were, while the toxicity level was demonstrated using ToxinPred server (Hasan et al, 2019b).…”

Proteome Exploration of Legionella pneumophila for Identifying Novel Therapeutics: A Hierarchical Subtractive Genomics and Reverse Vaccinology Approach

“…Reverse vaccinology approach usually identified a protein vaccine candidate using defined features, such as protein subcellular localization, topology, adhesion/antigenicity probability, epitopes, and its binding to the major histocompatibility complex (MHC) class I and II molecule [34]. Reverse vaccinology approach has been proven to prioritize and design vaccine targets against multiple pathogens [35][36][37][38][39].…”