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Infection and Immunity, July 2005, p. 4295-4301, Vol. 73, No. 7
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.7.4295-4301.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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

Sylvie Alonso,1,{dagger} Eve Willery,1 Genevieve Renauld-Mongénie,2 and Camille Locht1*

INSERM U629, Institut Pasteur de Lille, 1 rue du Prof. Calmette, F-59019 Lille, France,1 sanofi pasteur, Campus Mérieux, 1541 avenue Marcel Mérieux, F-69280 Marcy l'Etoile, France2

Received 8 December 2004/ Returned for modification 5 January 2005/ Accepted 3 March 2005

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.

* Corresponding author. Mailing address: INSERM U629, Institut Pasteur de Lille, 1 rue du Prof. Calmette, F-59019 Lille, France. Phone: (33) 3 20 87 11 51. Fax: (33) 3 20 87 11 58. E-mail: camille.locht{at}pasteur-lille.fr.

Editor: D. L. Burns

{dagger} Present address: Microbiology Department, National University of Singapore, Singapore.

Infection and Immunity, July 2005, p. 4295-4301, Vol. 73, No. 7
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.7.4295-4301.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Ho, S. Y., Chua, S. Q., Foo, D. G. W., Locht, C., Chow, V. T., Poh, C. L., Alonso, S. (2008). Highly Attenuated Bordetella pertussis Strain BPZE1 as a Potential Live Vehicle for Delivery of Heterologous Vaccine Candidates. Infect. Immun. 76: 111-119 [Abstract] [Full Text]  


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