Production of nontypeable Haemophilus influenzae HtrA by recombinant Bordetella pertussis with the use of filamentous hemagglutinin as a carrier

被引:10
作者
Alonso, S
Willery, E
Renauld-Mongénie, G
Locht, C
机构
[1] Inst Pasteur, INSERM, U629, F-59019 Lille, France
[2] Sanofi Pasteur, F-69280 Marcy Letoile, France
关键词
D O I
10.1128/IAI.73.7.4295-4301.2005
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 non-typeable Haemophilus influenzae to either FRA 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 FRA-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.
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页码:4295 / 4301
页数:7
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共 40 条
[11]   UREASE-ASSOCIATED HEAT-SHOCK PROTEIN OF HELICOBACTER-PYLORI [J].
EVANS, DJ ;
EVANS, DG ;
ENGSTRAND, L ;
GRAHAM, DY .
INFECTION AND IMMUNITY, 1992, 60 (05) :2125-2127
[12]   Evidence that a globular conformation is not compatible with FhaC-mediated secretion of the Bordetella pertussis filamentous haemagglutinin [J].
Guédin, S ;
Willery, E ;
Locht, C ;
Jacob-Dubuisson, F .
MOLECULAR MICROBIOLOGY, 1998, 29 (03) :763-774
[13]   Brief heat shock treatment induces a long-lasting alteration in the glycolipid receptor binding specificity and growth rate of Haemophilus influenzae [J].
Hartmann, E ;
Lingwood, C .
INFECTION AND IMMUNITY, 1997, 65 (05) :1729-1733
[14]   RESPONSE AND DECLINE OF SERUM IGG ANTIBODIES TO PERTUSSIS TOXIN, FILAMENTOUS HEMAGGLUTININ AND PERTACTIN IN CHILDREN WITH PERTUSSIS [J].
ISACSON, J ;
TROLLFORS, B ;
HEDVALL, G ;
TARANGER, J ;
ZACKRISSON, G .
SCANDINAVIAN JOURNAL OF INFECTIOUS DISEASES, 1995, 27 (03) :273-277
[15]   Invasion of human respiratory epithelial cells by Bordetella pertussis:: Possible role for a filamentous hemagglutinin Arg-Gly-Asp sequence and α5β1 integrin [J].
Ishibashi, Y ;
Relman, DA ;
Nishikawa, A .
MICROBIAL PATHOGENESIS, 2001, 30 (05) :279-288
[16]   Channel formation by FhaC, the outer membrane protein involved in the secretion of the Bordetella pertussis filamentous hemagglutinin [J].
Jacob-Dubuisson, F ;
El-Hamel, C ;
Saint, N ;
Guédin, S ;
Willery, E ;
Molle, G ;
Locht, C .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (53) :37731-37735
[17]   THE ROLE OF A STRESS-RESPONSE PROTEIN IN SALMONELLA-TYPHIMURIUM VIRULENCE [J].
JOHNSON, K ;
CHARLES, I ;
DOUGAN, G ;
PICKARD, D ;
OGAORA, P ;
COSTA, G ;
ALI, T ;
MILLER, I ;
HORMAECHE, C .
MOLECULAR MICROBIOLOGY, 1991, 5 (02) :401-407
[18]   CHARACTERIZATION OF MURINE LUNG INFLAMMATION AFTER INFECTION WITH PARENTAL BORDETELLA-PERTUSSIS AND MUTANTS DEFICIENT IN ADHESINS OR TOXINS [J].
KHELEF, N ;
BACHELET, CM ;
VARGAFTIG, BB ;
GUISO, N .
INFECTION AND IMMUNITY, 1994, 62 (07) :2893-2900
[19]   OTITIS-MEDIA [J].
KLEIN, JO .
CLINICAL INFECTIOUS DISEASES, 1994, 19 (05) :823-833
[20]   Nasal immunization induces Haemophilus influenzae-specific Th1 and Th2 responses with mucosal IgA and systemic IgG antibodies for protective immunity [J].
Kurono, Y ;
Yamamoto, M ;
Fujihashi, K ;
Kodama, S ;
Suzuki, M ;
Mogi, G ;
McGhee, JR ;
Kiyono, H .
JOURNAL OF INFECTIOUS DISEASES, 1999, 180 (01) :122-132