Identification of vaccine and drug targets in Shigella dysenteriae sd197 using reverse vaccinology approach

Shigellosis is characterized as diarrheal disease that causes a high mortality rate especially in children, elderly and immunocompromised patients. More recently, the World Health Organization advised safe vaccine designing against shigellosis due to the emergence of Shigella dysenteriae resistant strains. Therefore, the aim of this study is to identify novel drug targets as well as the design of the potential vaccine candidates and chimeric vaccine models against Shigella dysenteriae. A computational based Reverse Vaccinology along with subtractive genomics analysis is one of the robust approaches used for the prioritization of drug targets and vaccine candidates through direct screening of genome sequence assemblies. Herein, a successfully designed peptide-based novel highly antigenic chimeric vaccine candidate against Shigella dysenteriae sd197 strain is proposed. The study resulted in six epitopes from outer membrane WP_000188255.1 (Fe (3+) dicitrate transport protein FecA) that ultimately leads to the construction of twelve vaccine models. Moreover, V9 construct was found to be highly immunogenic, non-toxic, non-allergenic, highly antigenic, and most stable in terms of molecular docking and simulation studies against six HLAs and TLRS/MD complex. So far, this protein and multiepitope have never been characterized as vaccine targets against Shigella dysenteriae. The current study proposed that V9 could be a significant vaccine candidate against shigellosis and to ascertain that further experiments may be applied by the scientific community focused on shigellosis.

Putative antigenic proteins identified by comparative and subtractive reverse vaccinology in necrotic enteritis-causing Clostridium perfringens isolated from broiler chickens

Background Avian necrotic enteritis (NE) caused by Clostridium perfringens is a disease with a major economic impact, generating losses estimated to 6 billion of dollars annually for the poultry industry worldwide. The incidence of the disease is particularly on the rise in broiler chicken flocks eliminating the preventive use of antibiotics. To date, no alternative allows for the efficient prevention of NE and a control of the disease using a vaccinal strategy would be mostly prized. For this purpose, comparative and subtractive reverse vaccinology identifying putative immunogenic bacterial surface proteins is one of the most promising approaches. Results A comparative genomic study was performed on 16 C. perfringens strains isolated from healthy broiler chickens and from broilers affected with necrotic enteritis. Results showed that the analyzed genomes were composed of 155,700 distinct proteins from which 13% were identified as extracellular, 65% as cytoplasmic and 22% as part of the bacterial membrane. The evaluation of the immunogenicity of these proteins was determined using the prediction software VaxiJen®. Conclusions For the most part, proteins with the highest scores were associated with an extracellular localisation. For all the proteins analyzed, the combination of both the immunogenicity score and the localisation prediction led to the selection of 12 candidate proteins that were mostly annotated as hypothetical proteins. We describe 6 potential candidates of higher interest due to their antigenic potential, their extracellular localisation, and their possible role in virulence of C. perfringens.

Pan-Genome Reverse Vaccinology Approach for the Design of Multi-Epitope Vaccine Construct against Escherichia albertii

Escherichia albertii is characterized as an emerging pathogen, causing enteric infections. It is responsible for high mortality rate, especially in children, elderly, and immunocompromised people. To the best of our knowledge, no vaccine exists to curb this pathogen. Therefore, in current study, we aimed to identify potential vaccine candidates and design chimeric vaccine models against Escherichia albertii from the analysis of publicly available data of 95 strains, using a reverse vaccinology approach. Outer-membrane proteins (n = 4) were identified from core genome as vaccine candidates. Eventually, outer membrane Fimbrial usher (FimD) protein was selected as a promiscuous vaccine candidate and utilized to construct a potential vaccine model. It resulted in three epitopes, leading to the design of twelve vaccine constructs. Amongst these, V6 construct was found to be highly immunogenic, non-toxic, non-allergenic, antigenic, and most stable. This was utilized for molecular docking and simulation studies against six HLA and two TLR complexes. This construct can therefore be used for pan-therapy against different strains of E. albertii and needs to be tested in vitro and in vivo.