Application of genomics and proteomics for identification of bacterial gene products as potential vaccine candidates (original) (raw)
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Bioinformatics: use in bacterial vaccine discovery
Biotechniques, 2001
Bioinformatics has now become a common laboratory name for groups studying genomic sequences. It is composed of many different, yet interrelated scientific fields such as genomics, proteomics, and transcriptional profiling. The availability of complete genomic sequences, especially prokaryotic organisms, allows one to rapidly identify, analyze, and clone genes of interest. For bacterial vaccine discovery, one can "mine" the genomic sequence for potential surface targets using various algorithms, characterize these gene targets, and produce primers for cloning, all before one enters the wet laboratory. This review will focus on various genomic mining tools/algorithms available for predicting open reading frames and their associated annotation (if known), physical and functional characterization, and cellular localization. Finally, examples are given of how all of this is being used for the identification of potential bacterial vaccine candidates.
Proteomics and Bioinformatics Strategies to Design Countermeasures against Infectious Threat Agents
Journal of Chemical Information and Modeling, 2006
The potential devastation resulting from an intentional outbreak caused by biological warfare agents such as Brucella abortus and Bacillus anthracis underscores the need for next generation vaccines. Proteomics, genomics, and systems biology approaches coupled with the bacterial ghost (BG) vaccine delivery strategy offer an ideal approach for developing safer, cost-effective, and efficacious vaccines for human use in a relatively rapid time frame. Critical to any subunit vaccine development strategy is the identification of a pathogen's proteins with the greatest potential of eliciting a protective immune response. These proteins are collectively referred to as the pathogen's immunome. Proteomics provides high-resolution identification of these immunogenic proteins using standard proteomic technologies, Western blots probed with antisera from infected patients, and the pathogen's sequenced and annotated genome. Selected immunoreactive proteins can be then cloned and expressed in nonpathogenic Gram-negative bacteria. Subsequently, a temperature shift or chemical induction process is initiated to induce expression of the ΦX174 E-lysis gene, whose protein product forms an E tunnel between the inner and outer membrane of the bacteria, expelling all intracellular contents. The BG vaccine system is a proven strategy developed for many different pathogens and tested in a complete array of animal models. The BG vaccine system also has great potential for producing multiagent vaccines for protection to multiple species in a single formulation.
Proteomics for development of vaccine
Journal of …, 2011
The success of genome projects has provided us with a vast amount of information on genes of many pathogenic species and has raised hopes for rapid progress in combating infectious diseases, both by construction of new effective vaccines and by creating a new generation of therapeutic drugs. Proteomics, a strategy complementary to the genomic-based approach, when combined with immunomics (looking for immunogenic proteins) and vaccinomics (characterization of host response to immunization), delivers valuable information on pathogen-host cell interaction. It also speeds the identification and detailed characterization of new antigens, which are potential candidates for vaccine development. This review begins with an overview of the global status of vaccinology based on WHO data. The main part of this review describes the impact of proteomic strategies on advancements in constructing effective antibacterial, antiviral and anticancer vaccines. Diverse aspects of disease mechanisms and disease preventions have been investigated by proteomics.
Bioinformatics Approach for Cell Surface Antigen Search of Helicobacter pylori
Helicobacter pylori has been linked with the ulcers and cancer in human. We have reported 39 best cell surface antigens which could implement in vaccine research. By incorporating the reverse vaccinology methodology, several portals such as SignalP3.0, LipoP1.0, TMHMM, PSORTB, HLA Pred and BLASTP were involved along with genome sequence information for obtaining best scored vaccine candidates such as lipoprotein and cell wall anchored proteins which may be involved in subunit vaccine development programs.
Application of genomics in bacterial vaccine discovery: a decade in review
Current Opinion in Pharmacology, 2008
The combined power of genomics and proteomics has led to many advances in the discovery of bacterial vaccine targets. The 'Holy Grail' for a vaccine is to be pathogen specific yet conserved among all strains, so that universal coverage is possible with the minimal number of antigens. Genomics allows us to target conserved proteins, while proteomics tells us what is actually expressed and what is accessible to antibodies. Achievements using these latest approaches are exemplified by the vaccine clinical trials that are ongoing for protein targets against Neiserria meningitidis and Staphylococcus aureus along with promising discoveries that have been made for other pathogens including Streptococcus pneumoniae and Streptococcus pyogenes. These developments are discussed in this review.
Proteomic technology in the design of new effective antibacterial vaccines
Expert Review of Proteomics, 2009
Infectious diseases still remain the main cause of human premature deaths, especially in developing countries. Vaccines constitute the most cost-effective tool for prophylaxis of infectious diseases. Elucidation of the complete genomes of many bacterial pathogens has provided a new blueprint for the search of novel vaccine candidates. At the same time, it was a turning point in the development of transcriptomics and proteomics. This article concentrates on the proteomic contribution to vaccinology, pointing out relationships between genomic, transcriptomic and proteomic approaches and describing how they complement one another. It also highlights the recent proteomic techniques applied to antigen identification, their capabilities and limitations, as well as the strategies that are taken to overcome technical difficulties and to refine applied methods. Finally, some recent experimental data concerning the proteomic/immunoproteomic influence on identification of vaccine candidates to prevent human infections caused by Streptococcus spp., as well as by a major bioterrorist agent, Bacillus anthracis is presented.
Molecular & Cellular Proteomics, 2003
Helicobacter pylori is a causative agent of severe diseases of the gastric tract ranging from chronic gastritis to gastric cancer. Cellular proteins of H. pylori were separated by high resolution two-dimensional gel electrophoresis. A dataset of 384 spots was automatically picked, digested, spotted, and analyzed by matrix-assisted laser desorption ionization mass spectrometry peptide mass fingerprint in triple replicates. This procedure resulted in 960 evaluable mass spectra. Using a new version of our data analysis software MS-Screener we improved identification and tested reliability of automatically generated data by comparing with manually produced data. Antigenic proteins from H. pylori are candidates for vaccines and diagnostic tests. Previous immunoproteomics studies of our group revealed antigen candidates, and 24 of them were now closely analyzed using the MS-Screener software. Only in three spots minor components were found that may have influenced their antigenicities. These findings affirm the value of immunoproteomics as a hypothesis-free approach. Additionally, the protein species distribution of the known antigen GroEL was investigated, dimers of the protein alkyl hydroperoxide reductase were found, and the fragmentation of ␥-glutamyltranspeptidase was demonstrated.
Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 2015
Helicobacter pylori (H. pylori) is an important pathogen associated with diverse gastric disorders ranging from peptic ulcer to malignancy. It has also been recognized by the World Health Organization (WHO) as class I carcinogen. Conventional treatment regimens for H. pylori seem to be ineffective, possibly due to antibiotic resistance mechanisms acquired by the pathogen. In this study we have successfully employed a reverse vaccinology approach to predict the potential vaccine candidates against H. pylori. The predicted potential vaccine candidates include vacA, babA, sabA, fecA and omp16. Host-pathogen interactions analysis elaborated their direct or indirect role in the specific signaling pathways including epithelial cell polarity, metabolism, secretion system and transport. Furthermore, surface-exposed antigenic epitopes were predicted and analyzed for conservation among 39 complete genomes of H. pylori (Genbank) for all the candidate proteins. These epitopes may serve as a bas...
2021
Amidst the surge in the prevalence of resistant H. pylori infections, WHO in 2017 has given a high priority to clarithromycin-resistant H. pylori for research and to develop new antibacterial agents. In this study, the Helicobacter pylori 26695 strain was investigated with extensive computational biology applications to identify novel therapeutic drug targets or vaccine candidates. During the proteomic functional annotation of an organism, it is crucial to determine the function of proteins. The pathogen-specific pathways were found to include only twelve proteins, paving the way further to determine drug or vaccine targets. Lipoprotein A-4’-phosphatase (LpxF) was found to be a novel vaccine target with the highest antigenicity. Having broad-spectrum conservancy with other H. pylori strains. Further, an immunoinformatic approach was used to predict an effective epitope-based vaccine against H. pylori. LpxF protein has been predicted to have linear and conformational B-cell epitopes ...
Protectome analysis: a new selective bioinformatics tool for bacterial vaccine candidate discovery.
New generation vaccines are demanded to include only the key antigens sufficient to confer protective immunity among the plethora of pathogen molecules. In the last decade large-scale genomics-based technologies emerged. Among them, the Reverse Vaccinology approach was successfully applied to the development of an innovative vaccine against Neisseria meningitidis serogroup B, now available in the marked with the commercial name BEXSERO (Novartis Vaccines). The limiting step of such approaches is the number of antigens to be tested in in vivo models. Several laboratories have been trying to refine the original approach in order to get to the identification of the relevant antigens straight from the genome. Here we report a new bioinformatics tool which moves a first step in this direction. The tool has been developed by identifying structural/functional features recurring in known bacterial protective antigens, the so called Protectome space, and using such protective signatures for protective antigen discovery. In particular, we applied this new approach to Staphylococcus aureus and Group B Streptococcus and we show that not only already known protective antigens were re-discovered, but also two new were identified.