Immunoproteomic analysis of Bordetella pertussis and identification of new immunogenic proteins

Altındiş, Emrah; Tefon, Burcu E.; Yıldırım, Volkan; Özcengīz, Erkan; Becher, Dörte; Hecker, Michael; Özcengiz, Gülay

doi:10.1016/j.vaccine.2008.11.020

Cited by 47 publications

(47 citation statements)

References 60 publications

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“…Other possible candidate protective antigens include the iron-repressible outer membrane proteins (5), lipopolysaccharide (LPS) (24), and autotransporters like BrKA (29). Utilizing immunoproteomics, multiple novel antigens from B. pertussis extracts that are recognized by immune sera were identified recently (1). Taken together, the results of this study and other studies highlight the synergistic contribution of known and yet-to-be-identified proteins in maximizing protection against B. pertussis.…”

Section: Discussionmentioning

confidence: 62%

Cross-Species Protection Mediated by a Bordetella bronchiseptica Strain Lacking Antigenic Homologs Present in Acellular Pertussis Vaccines

Sukumar¹,

Sloan²,

Conover

et al. 2010

Infect Immun

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The Bordetella species are Gram-negative bacterial pathogens that are characterized by long-term colonization of the mammalian respiratory tract and are causative agents of respiratory diseases in humans and animals. Despite widespread and efficient vaccination, there has been a world-wide resurgence of pertussis, which remains the leading cause of vaccine-preventable death in developed countries. It has been proposed that current acellular vaccines (Pa) composed of only a few bacterial proteins may be less efficacious because of vaccine-induced antigenic shifts and adaptations. To gain insight into the development of a newer generation of vaccines, we constructed a Bordetella bronchiseptica strain (LPaV) that does not express the antigenic homologs included in any of the Pa vaccines currently in use. This strain also lacks adenylate cyclase toxin, an essential virulence factor, and BipA, a surface protein. While LPaV colonized the mouse nose as efficiently as the wild-type strain, it was highly deficient in colonization of the lower respiratory tract and was attenuated in induction of inflammation and injury to the lungs. Strikingly, to our surprise, we found that in an intranasal murine challenge model, LPaV elicited cross-species protection against both B. bronchiseptica and Bordetella pertussis. Our data suggest the presence of immunogenic protective components other than those included in the pertussis vaccine. Combined with the whole-genome sequences of many Bordetella spp. that are available, the results of this study should serve as a platform for strategic development of the next generation of acellular pertussis vaccines.

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Section: Discussionmentioning

confidence: 62%

Cross-Species Protection Mediated by a Bordetella bronchiseptica Strain Lacking Antigenic Homologs Present in Acellular Pertussis Vaccines

Sukumar¹,

Sloan²,

Conover

et al. 2010

Infect Immun

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“…23 Proteome of B. pertussis based on 2-DE have been studied to clarify the pathogenesis and immune mechanisms of pertussis. 24,25 In this study, proteomic technology was applied to clarify the composition of the co-purified APVs and compared the consistency of products between different batches and between different manufactures. A 2-DE protocol was developed to effectively resolve the protein mixture of the samples and subsequently protein spots were identified by MALDI-TOF/TOF MS.…”

Section: Discussionmentioning

confidence: 99%

Characterization of co-purified acellular pertussis vaccines

Tan

Asokanathan

et al. 2015

Human Vaccines & Immunotherapeutics

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These authors contributed equally to this work.Keyword: Co-purified acellular pertussis vaccines, immune responses, protection, proteomic analysis Abbreviations: WPVs, whole-cell pertussis vaccines; APVs, acellular pertussis vaccines; PT, pertussis toxin; FHA, filamentous hemagglutinin; 2-DE, 2-dimensional gel electrophoresis; PRN, pertactin; FIM, fimbriae; BipA, putative outer membrane ligand binding protein; Sbp, sulfate-binding protein precursor; sphB1, autotransporter subtilisin-like protease; bvg, Bordetella virulence regulon; SHD, single human doseWhole-cell pertussis vaccines (WPVs) have been completely replaced by the co-purified acellular vaccines (APVs) in China. To date few laboratory studies were reported for co-purified APVs in terms of their antigenic composition and protective immune responses. To further understand the antigenic composition in co-purified APVs, in the present study 2-dimensional gel electrophoresis-based proteomic technology was used to analyze the composition of copurified APVs. The results showed that besides the main antigens pertussis toxin (PT) and filamentous hemagglutinin (FHA), co-purified APVs also contained pertactin (PRN), fimbriae (FIM) 2and3 and other minor protein antigens. Of the 9 proteins identified, 3 were differentially presented in products from manufacturer 1 and manufacturer 2. Compared with WPVs and purified APVs, co-purified APVs induced a mixed Th1/Th2 immune response with more toward to a Th1 response than the purified APVs in this study. These results hint that different immune mechanisms might be involved in protection induced by co-purified and purified APVs.

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“…Immunoproteomics has also been used to identify novel antigens that elicit an immune response, as recently reviewed (5), but when used in isolation, it has limitations, and no efficacious antigens have yet been identified by using this approach. Indeed, the confirmed prophylactic Bordetella pertussis antigen filamentous hemagglutinin (FHA), a component of most licensed acellular whooping cough vaccines, was undetectable in two immunoproteomic studies (6,7).…”

mentioning

confidence: 99%

Linocin and OmpW Are Involved in Attachment of the Cystic Fibrosis-Associated Pathogen Burkholderia cepacia Complex to Lung Epithelial Cells and Protect Mice against Infection

McClean¹,

Healy

Collins³

et al. 2016

Infect Immun

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Members of the Burkholderia cepacia complex (Bcc) cause chronic opportunistic lung infections in people with cystic fibrosis (CF), resulting in a gradual lung function decline and, ultimately, patient death. The Bcc is a complex of 20 species and is rarely eradicated once a patient is colonized; therefore, vaccination may represent a better therapeutic option. We developed a new proteomics approach to identify bacterial proteins that are involved in the attachment of Bcc bacteria to lung epithelial cells. Fourteen proteins were reproducibly identified by two-dimensional gel electrophoresis from four Bcc strains representative of two Bcc species: Burkholderia cenocepacia, the most virulent, and B. multivorans, the most frequently acquired. Seven proteins were identified in both species, but only two were common to all four strains, linocin and OmpW. Both proteins were selected based on previously reported data on these proteins in other species. Escherichia coli strains expressing recombinant linocin and OmpW showed enhanced attachment (4.2-and 3.9-fold) to lung cells compared to the control, confirming that both proteins are involved in host cell attachment. Immunoproteomic analysis using serum from Bcc-colonized CF patients confirmed that both proteins elicit potent humoral responses in vivo. Mice immunized with either recombinant linocin or OmpW were protected from B. cenocepacia and B. multivorans challenge. Both antigens induced potent antigen-specific antibody responses and stimulated strong cytokine responses. In conclusion, our approach identified adhesins that induced excellent protection against two Bcc species and are promising vaccine candidates for a multisubunit vaccine. Furthermore, this study highlights the potential of our proteomics approach to identify potent antigens against other difficult pathogens.

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Immunoproteomic analysis of Bordetella pertussis and identification of new immunogenic proteins

Cited by 47 publications

References 60 publications

Cross-Species Protection Mediated by a Bordetella bronchiseptica Strain Lacking Antigenic Homologs Present in Acellular Pertussis Vaccines

Cross-Species Protection Mediated by a Bordetella bronchiseptica Strain Lacking Antigenic Homologs Present in Acellular Pertussis Vaccines

Characterization of co-purified acellular pertussis vaccines

Linocin and OmpW Are Involved in Attachment of the Cystic Fibrosis-Associated Pathogen Burkholderia cepacia Complex to Lung Epithelial Cells and Protect Mice against Infection

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