scholarly journals Production of Nontypeable Haemophilus influenzae HtrA by Recombinant Bordetella pertussis with the Use of Filamentous Hemagglutinin as a Carrier

2005 ◽  
Vol 73 (7) ◽  
pp. 4295-4301 ◽  
Author(s):  
Sylvie Alonso ◽  
Eve Willery ◽  
Genevieve Renauld-Mongénie ◽  
Camille Locht
Keyword(s):  
Immune Responses ◽  
Haemophilus Influenzae ◽  
Bordetella Pertussis ◽  
Whooping Cough ◽  
Etiologic Agent ◽  
Nontypeable Haemophilus Influenzae ◽  
Bacterial Surface ◽  
Filamentous Hemagglutinin ◽  
Bacterial Vector ◽  
Antibody Titers

ABSTRACT Bordetella pertussis, the etiologic agent of whooping cough, is a highly infectious human pathogen capable of inducing mucosal and systemic immune responses upon a single intranasal administration. In an attenuated, pertussis toxin (PTX)-deficient recombinant form, it may therefore constitute an efficient bacterial vector that is particularly well adapted for the delivery of heterologous antigens to the respiratory mucosa. Filamentous hemagglutinin (FHA) has been used as a carrier to present foreign antigens at the bacterial surface, thereby inducing local, systemic, and protective immune responses to these antigens in mice. Both full-length and truncated (Fha44) forms of FHA have been used for antigen presentation. To investigate the effect of the carrier (FHA or Fha44) on antibody responses to passenger antigens, we genetically fused the HtrA protein of nontypeable Haemophilus influenzae to either FHA form. The fha-htrA and Fha44 gene-htrA hybrids were expressed as single copies inserted into the chromosome of PTX-deficient B. pertussis. Both chimeras were secreted into the culture supernatants of the recombinant strains and were recognized by anti-FHA and anti-HtrA antibodies. Intranasal infection with the strain producing the FHA-HtrA hybrid led to significantly higher anti-HtrA and anti-FHA antibody titers than those obtained in mice infected with the Fha44-HtrA-producing strain. Interestingly, the B. pertussis strain producing the Fha44-HtrA chimera colonized the mouse lungs more efficiently than the parental, Fha44-producing strain and gave rise to higher anti-FHA antibody titers than those induced by the parental strain.

scholarly journals Bordetella pertussis filamentous hemagglutinin interacts with a leukocyte signal transduction complex and stimulates bacterial adherence to monocyte CR3 (CD11b/CD18).

1994 ◽  
Vol 180 (4) ◽  
pp. 1225-1233 ◽  
Author(s):  
Y Ishibashi ◽  
S Claus ◽  
D A Relman
Keyword(s):  
Signal Transduction ◽  
Bordetella Pertussis ◽  
Whooping Cough ◽  
Bacterial Pathogen ◽  
Binding Activity ◽  
Host Cells ◽  
Bacterial Surface ◽  
Filamentous Hemagglutinin ◽  
Complement Receptor 3 ◽  
Leukocyte Response

Bordetella pertussis, the causative agent of whooping cough, adheres to human monocytes/macrophages by means of a bacterial surface-associated protein, filamentous hemagglutinin (FHA) and the leukocyte integrin, complement receptor 3 (CR3, alpha M beta 2, CD11b/CD18). We show that an FHA Arg-Gly-Asp site induces enhanced B. pertussis binding to monocytes, and that this enhancement is blocked by antibodies directed against CR3. Enhancement requires a monocyte signal transduction complex, composed of leukocyte response integrin (alpha? beta 3) and integrin-associated protein (CD47). This complex is known to upregulate CR3 binding activity. Thus, a bacterial pathogen enhances its own attachment to host cells by coopting a host cell signaling pathway.

scholarly journals Evidence of functional cell-mediated immune responses to nontypeable Haemophilus influenzae in otitis-prone children

PLoS ONE ◽  
2018 ◽  
Vol 13 (4) ◽  
pp. e0193962 ◽  
Author(s):  
Elke Seppanen ◽  
Dino Tan ◽  
Karli J. Corscadden ◽  
Andrew J. Currie ◽  
Peter C. Richmond ◽  
...  
Keyword(s):  
Immune Responses ◽  
Haemophilus Influenzae ◽  
Nontypeable Haemophilus Influenzae

scholarly journals Construction and Immunogenicity of Recombinant Adenovirus Vaccines Expressing the HMW1, HMW2, or Hia Adhesion Protein of Nontypeable Haemophilus influenzae

2010 ◽  
Vol 17 (10) ◽  
pp. 1567-1575 ◽  
Author(s):  
Linda E. Winter ◽  
Stephen J. Barenkamp
Keyword(s):  
Haemophilus Influenzae ◽  
Vaccine Development ◽  
Recombinant Adenovirus ◽  
Serum Antibody ◽  
Nontypeable Haemophilus Influenzae ◽  
Hek 293 ◽  
Adhesion Protein ◽  
Protective Antigens ◽  
Antibody Titers ◽  
Adenoviral Construct

ABSTRACT The objective of the present study was to construct and assess the immunogenicity of recombinant adenovirus vectors expressing the HMW1, HMW2, or Hia protein of nontypeable Haemophilus influenzae (NTHi). These proteins are critical adhesins and potential protective antigens expressed by NTHi. Segments of the hmw1A and hmw2A structural genes that encode the distal one-half of mature HMW1 or HMW2 were cloned into the T7 expression vector pGEMEX-2. These constructs encoded stable HMW1 or HMW2 recombinant fusion protein that expresses B-cell epitopes common to most NTHi strains. A segment of the hia gene that encodes the surface-exposed portion of mature Hia was also cloned into pGEMEX-2. The resulting T7 gene 10 translational fusions were excised from the parent plasmids and cloned into the shuttle plasmid pDC316. Cotransfection of HEK 293 cells with the pDC316 derivatives and pBHGloxΔE1,3Cre resulted in the production of viral plaques from which recombinant adenoviruses expressing fusion proteins were recovered. Chinchillas immunized intraperitoneally with a single 108-PFU dose of either the HMW2 or Hia adenoviral construct developed high anti-HMW2 or anti-Hia serum antibody titers within 4 weeks of immunization. Chinchillas immunized intranasally with a single 107- to 109-PFU dose of the Hia adenoviral construct also developed high anti-Hia serum antibody titers within 8 weeks of immunization. Recombinant adenoviruses represent a promising system to induce mucosal and systemic immunity and protection against mucosal diseases such as otitis media. Recombinant adenoviruses expressing recombinant HMW1, HMW2, or Hia protein will be important new tools in NTHi vaccine development efforts.

scholarly journals Filamentous Hemagglutinin of Bordetella bronchiseptica Is Required for Efficient Establishment of Tracheal Colonization

1998 ◽  
Vol 66 (12) ◽  
pp. 5921-5929 ◽  
Author(s):  
Peggy A. Cotter ◽  
Ming H. Yuk ◽  
Seema Mattoo ◽  
Brian J. Akerley ◽  
Jeff Boschwitz ◽  
...  
Keyword(s):  
Whooping Cough ◽  
Ectopic Expression ◽  
Etiologic Agent ◽  
Bordetella Bronchiseptica ◽  
Host Animal ◽  
Filamentous Hemagglutinin ◽  
Unanesthetized Animals ◽  
Necessary And Sufficient

ABSTRACT Adherence to ciliated respiratory epithelial cells is considered a critical early step in Bordetella pathogenesis. ForBordetella pertussis, the etiologic agent of whooping cough, several factors have been shown to mediate adherence to cells and cell lines in vitro. These putative adhesins include filamentous hemagglutinin (FHA), fimbriae, pertactin, and pertussis toxin. Determining the precise roles of each of these factors in vivo, however, has been difficult, due in part to the lack of natural-host animal models for use with B. pertussis. Using the closely related species Bordetella bronchiseptica, and by constructing both deletion mutation and ectopic expression mutants, we have shown that FHA is both necessary and sufficient for mediating adherence to a rat lung epithelial (L2) cell line. Using a rat model of respiratory infection, we have shown that FHA is absolutely required, but not sufficient, for tracheal colonization in healthy, unanesthetized animals. FHA was not required for initial tracheal colonization in anesthetized animals, however, suggesting that its role in establishment may be dedicated to overcoming the clearance action of the mucociliary escalator.

scholarly journals Bordetella pertussis Filamentous Hemagglutinin Enhances the Immunogenicity of Liposome-Delivered Antigen Administered Intranasally

1998 ◽  
Vol 66 (4) ◽  
pp. 1764-1767 ◽  
Author(s):  
Odile Poulain-Godefroy ◽  
Nathalie Mielcarek ◽  
Nathalie Ivanoff ◽  
Franck Remoué ◽  
Anne-Marie Schacht ◽  
...  
Keyword(s):  
Immune Response ◽  
Bordetella Pertussis ◽  
Humoral Immune Response ◽  
Dependent Manner ◽  
Humoral Immune ◽  
Filamentous Hemagglutinin ◽  
Antibody Titers ◽  
Suboptimal Dose ◽  
Outbred Mice ◽  
Dose Dependent

ABSTRACT In an attempt to increase the immunogenicity of mucosally delivered antigens, we incorporated the Bordetella pertussisfilamentous hemagglutinin (FHA) adhesin into liposomes containing the glutathione S-transferase of Schistosoma mansoni (Sm28GST) as a model antigen. Outbred mice immunized twice intranasally with liposomes containing a constant suboptimal dose of Sm28GST and increasing doses of FHA produced anti-Sm28GST antibodies in a FHA dose-dependent manner. The addition of 3 μg of FHA to the liposomes induced more than 10-fold-higher anti-Sm28GST antibody titers, compared to those induced by liposomes without FHA. The presence of FHA did not alter the nature of the humoral immune response, and the sera contained anti-Sm28GST immunoglobulin G1 (IgG1), IgG2a, and IgG2b. However, anti-Sm28GST IgA was only detected when at least 3 μg of FHA was added to the preparation. These results show a promising potential for FHA to enhance the immunogenicity of mucosally administered antigens incorporated into liposomes.

Sign in / Sign up

Export Citation Format

Share Document