Identification of vaccine candidate antigens from a genomic analysis of Porphyromonas gingivalis

Ross, Bruce C.; Czajkowski, L.; Hocking, Dianna M; Margetts, Mai B.; Webb, Elizabeth; Rothel, Linda; Patterson, Michelle; Agius, C.; Camuglia, Sarina; Reynolds, Eric C.; Littlejohn, Tim; Gaëta, Bruno; Ng, Albert; Kuczek, Elizabeth; Mattick, John S.; Gearing, David P.; Barr, Ian G.

doi:10.1016/s0264-410x(01)00173-6

Cited by 130 publications

(78 citation statements)

References 17 publications

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“…The third group of proteins identified were predicted to be integral Omps. Of these, five (Tlr [6], RagA [9], P90, P92 and P93) were classified as TOMRs, due to their overall sequence similarity to known TOMRs and the presence of the TonB box III motif [9,12,37]. TOMRs contain a large β-barrel domain that is integral to the OM [38].…”

Section: P Gingivalis Major Ompsmentioning

confidence: 99%

Major outer membrane proteins and proteolytic processing of RgpA and Kgp of Porphyromonas gingivalis W50

Veith

Talbo

Slakeski

et al. 2002

Biochemical Journal

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Porphyromonas gingivalis is an anaerobic, asaccharolytic Gram-negative rod associated with chronic periodontitis. We have undertaken a proteomic study of the outer membrane of P. gingivalis strain W50 using two-dimensional gel electrophoresis and peptide mass fingerprinting. Proteins were identified by reference to the pre-release genomic sequence of P. gingivalis available from The Institute for Genomic Research. Out of 39 proteins identified, five were TonB-linked outer membrane receptors, ten others were putative integral outer membrane proteins and four were putative lipoproteins. Pyroglutamate was found to be the N-terminal residue of seven of the proteins, and was predicted to be the N-terminal residue of 13 additional proteins. The RgpA, Kgp and HagA polyproteins were identified as fully processed domains in outer membranes prepared in the presence of proteinase inhibitors. Several domains were found to be C-terminally truncated 16–57 residues upstream from the N-terminus of the following domain, at a residue penultimate to a lysine. This pattern of C-terminal processing was not detected in a W50 strain isogenic mutant lacking the lysine-specific proteinase Kgp. Construction of another W50 isogenic mutant lacking the arginine-specific proteinases indicated that RgpB and/or RgpA were also involved in domain processing. The C-terminal adhesin of RgpA, designated RgpA27, together with RgpB and two newly identified proteins designated P27 and P59 were found to migrate on two-dimensional gels as vertical streaks at a molecular mass 13–42kDa higher than that calculated from their gene sequences. The electrophoretic behaviour of these proteins, together with their immunoreactivity with a monoclonal antibody that recognizes lipopolysaccharide, is consistent with a modification that could anchor the proteins to the outer membrane.

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Section: P Gingivalis Major Ompsmentioning

confidence: 99%

Major outer membrane proteins and proteolytic processing of RgpA and Kgp of Porphyromonas gingivalis W50

Veith

Talbo

Slakeski

et al. 2002

Biochemical Journal

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“…This process is independent of several of the constraints of classical vaccinology, such as the need to culture the pathogen in vitro. Genome-based vaccine discovery projects have since been initiated for a range of pathogens, including Streptococcus agalactiae (18), Streptococcus pneumoniae (19), Porphyromonas gingivalis (20), Chlamydia pneumoniae (21), Bacillus anthracis (22,23), and Brucella melitensis (24). These projects are based on stand-alone reverse vaccinology approaches, refined reverse vaccinology approaches (e.g., using pangenomics), and/or a combination of genomic, proteomic, and transcriptomic approaches.…”

Section: Reverse Vaccinologymentioning

confidence: 99%

Vaccinology in the genome era

Rinaudo¹,

Telford²,

Rappuoli³

et al. 2009

J. Clin. Invest.

144

118

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Vaccination has played a significant role in controlling and eliminating life-threatening infectious diseases throughout the world, and yet currently licensed vaccines represent only the tip of the iceberg in terms of controlling human pathogens. However, as we discuss in this Review, the arrival of the genome era has revolutionized vaccine development and catalyzed a shift from conventional culture-based approaches to genome-based vaccinology. The availability of complete bacterial genomes has led to the development and application of high-throughput analyses that enable rapid targeted identification of novel vaccine antigens. Furthermore, structural vaccinology is emerging as a powerful tool for the rational design or modification of vaccine antigens to improve their immunogenicity and safety.

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“…These candidates were reduced to a set 40 proteins, which were purified and used to immunized mice that were subsequently challenged with live bacteria in a subcutaneous abscess model. Two antigens demonstrated protection in this model of infection and therefore could represent potential vaccine candidates [48] Streptococcus agalactiae (Group B streptococcus)…”

Section: Neisseria Meningitidis B Major Cause Of Bacterial Septicemiamentioning

confidence: 99%

Post‐genomic vaccine development

2006

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For over a century, vaccines were developed according to Pasteur's principles of isolating, inactivating and injecting the causative agent of an infectious disease. The availability of a complete microbial genome sequence in 1995 marked the beginning of a genomic era that has allowed scientists to change the paradigm and approach vaccine development starting from genomic information, a process named reverse vaccinology. This can be considered as one of the most powerful examples of how genomic information can be used to develop therapeutic interventions, which were difficult or impossible to tackle with conventional approaches. As the genomic era progressed, it became apparent that multi-strain genome analysis is fundamental to the design of universal vaccines. In the post-genomic era, the next challenge of the vaccine biologist will be the merging of the vaccinology with structural biology.

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Identification of vaccine candidate antigens from a genomic analysis of Porphyromonas gingivalis

Cited by 130 publications

References 17 publications

Major outer membrane proteins and proteolytic processing of RgpA and Kgp of Porphyromonas gingivalis W50

Major outer membrane proteins and proteolytic processing of RgpA and Kgp of Porphyromonas gingivalis W50

Vaccinology in the genome era

Post‐genomic vaccine development

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