Proteomic technology in the design of new effective antibacterial vaccines (original) (raw)
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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.
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.
Vaccine, 2000
The ability of bioinformatics to characterize genomic sequences from pathogenic bacteria for prediction of genes that may encode vaccine candidates, e.g. surface localized proteins, has been evaluated. By applying appropriate tools for genomic mining to the published sequence of Haemophilus influenzae Rd genome, it was possible to identify a putative vaccine candidate, the outer membrane lipoprotein, P6. Proteomics complements genomics by offering abilities to rapidly identify the products of predicted genes, e.g. proteins in outer membrane preparations. The ability to identify the P6 protein uniquely from entries in a sequence database from the expected peptide-mass fingerprint of P6 demonstrates the power of proteomics. The application of proteomics for identification of vaccine candidates for another pathogenic bacterium, Helicobacter pylori using two different approaches is described. The first involves rapid identification of a series of monoclonal antibody reactive proteins from N-terminal sequence tags. The other approach involves identification of proteins in outer membrane preparations by 2-D electrophoresis followed by trypsin digestion and peptide mass map analysis. Our combined studies demonstrate that utilization of genome sequences by application of bioinformatics through genomics and proteomics can expedite the vaccine discovery process by rapidly providing a set of potential candidates for further testing.
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.
Impact of proteomics on anti-Mycobacterium tuberculosis (MTB) vaccine development
Polish journal of microbiology / Polskie Towarzystwo Mikrobiologów = The Polish Society of Microbiologists, 2009
Tuberculosis is a serious infection disease which causes more than two million deaths annually. The TB pandemic has continued despite widespread use of the only available licensed TB vaccine--Bacillus Calmette-Guerin (BCG). Additionally, the increasing incidences of multidrug resistant strains and coinfection with HIV mean that tuberculosis constitutes a growing global threat. Thus, improvement of the vaccination strategy against TB is an urgent need, requiring international cooperation of the research community. The completion of many mycobacterial genome sequences has greatly facilitated the global analysis at the transcriptome and proteome level. This in consequence has accelerated progress in the vaccinology field resulting in identification of a large numbers of antigens with potential in TB vaccines. This review concentrates on the proteomic contribution to TB vaccinology. At the end of the article some recent achievements of structural proteomics and developing an epitope-dri...
Genomics, proteomics & bioinformatics, 2004
In this review, we advance a new concept in developing vaccines and/or drugs to target specific proteins expressed during the early stage of Bacillus anthracis (anthrax) infection and address existing challenges to this concept. Three proteins (immune inhibitor A, GPR-like spore protease, and alanine racemase) initially identified by proteomics in our laboratory were found to have differential expressions during anthrax spore germination and early outgrowth. Other studies of different bacillus strains indicate that these three proteins are involved in either germination or cytotoxicity of spores, suggesting that they may serve as potential targets for the design of anti-anthrax vaccines and drugs.
Molecular & Cellular …, 2012
We propose an experimental strategy for highly accurate selection of candidates for bacterial vaccines without using in vitro and/or in vivo protection assays. Starting from the observation that efficacious vaccines are constituted by conserved, surface-associated and/or secreted components, the strategy contemplates the parallel application of three high throughput technologies, i.e. mass spectrometry-based proteomics, protein array, and flowcytometry analysis, to identify this category of proteins, and is based on the assumption that the antigens identified by all three technologies are the protective ones. When we tested this strategy for Group A Streptococcus, we selected a total of 40 proteins, of which only six identified by all three approaches. When the 40 proteins were tested in a mouse model, only six were found to be protective and five of these belonged to the group of antigens in common to the three technologies. Finally, a combination of three protective antigens conferred broad protection against a panel of four different Group A Streptococcus strains. This approach may find general application as an accelerated and highly accurate path to bacterial vaccine discovery.
Proteomics Technology Applied to Upstream and Downstream Process Development of a Protein Vaccine
D evelopment and manufacturing of recombinant-protein–based vaccines has in the past few years become very similar to that of other well-documented and well-characterized biological drugs. For investigational vaccines, chemistry, manufacturing, and controls (CMC) information is critical for a successful regulatory filing. The process development and CGMP manufacturing of a recombinant protein drug is on the critical path toward clinical phase 1 dosing and safety studies as well as proof-of-concept clinical studies (1, 2). However, resources invested in this process may be wasted if the methods and results are not sufficiently documented. Here we describe how proteomics technology has enabled a scientific, risk-based framework for implementing process analytical technology (PAT) in the development of a well-characterized protein vaccine. Our aim is to identify the scientific tools that support innovation in process development and to exemplify the strategy for regulatory implementati...
Nature Biotechnology, 2006
We describe a proteomic approach for identifying bacterial surface-exposed proteins quickly and reliably for their use as vaccine candidates. Whole cells are treated with proteases to selectively digest protruding proteins that are subsequently identified by mass spectrometry analysis of the released peptides. When applied to the sequenced M1_SF370 group A Streptococcus strain, 68 PSORT-predicted surface-associated proteins were identified, including most of the protective antigens described in the literature. The number of surface-exposed proteins varied from strain to strain, most likely as a consequence of different capsule content. The surface-exposed proteins of the highly virulent M23_DSM2071 strain included 17 proteins, 15 in common with M1_SF370. When 14 of the 17 proteins were expressed in E. coli and tested in the mouse for their capacity to confer protection against a lethal dose of M23_DSM2071, one new protective antigen (Spy0416) was identified. This strategy overcomes the difficulties so far encountered in surface protein characterization and has great potential in vaccine discovery.