Novel recombinant bordetella strains

A Bordetella, strain technology, applied in antibacterial drugs, drug combinations, viruses/phages, etc., can solve problems such as unusability

Active Publication Date: 2015-09-23
INST NAT DE LA SANTE & DE LA RECHERCHE MEDICALE (INSERM)
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Unfortunately, the addition of this adjuvant to nasal vaccine formulations has caused Bell's palsy (Mutsch et al., 2004) and therefore cannot be used in humans

Method used

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  • Novel recombinant bordetella strains
  • Novel recombinant bordetella strains
  • Novel recombinant bordetella strains

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[0104] Materials and Methods

[0105] Bacterial strains and growth conditions. The B. pertussis strains used in this study are listed in Table 1. They were cultured at 37°C in goat blood supplemented with 1% glycerol, 20% defibrinated, and 100 μg / ml streptomycin (Sigma Chemical Co., St Louis, Mo.) Grow on Bordet-Gengou agar (Difco, Detroit, Mich.) for 72 h. Liquid cultures of B. pertussis were prepared as previously described (Menozzi et al., 1991) in the presence of 1 g / L of hepta(2,6-di-o-methyl)β-cyclodextrin ( Sigma) in Steiner-Scholte (Stainer-Scholte) medium (Stainer and Scholte, 1970).

[0106] Construction of plasmids and recombinant BPZE1 strains. The different BPZE1 derivatives described here all contain a transgene in the dnt locus of BPZE1 by using a gene derived from pJQmp200rpsL12 (Quandt and Hynes, 1993) and containing the upstream and downstream of the dnt gene. The plasmid for the region was subjected to allelic exchange for insertion as described (Mier...

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Abstract

The present invention relates to a recombinant genetically attenuated Bordetella strain expressing a hybrid protein comprising the N-terminal fragment of filamentous haemagglutinin (FHA) and a heterologous epitope or antigenic protein or protein fragment, different from FHA, wherein the gene coding for the native FHA protein is inactivated. The Bordetella strain is preferably a Bordetella pertussis strain, but may also be another Bordetella species, such as Bordetella bronchiseptica, Bordetella parapertussis or Bordetella avium. The invention further provides a life attenuated vaccine for the treatment of a mucosal or systemic infectious disease comprising a Bordetella strain as defined above intended to elicit a immune response against pathogens responsible for systemic or mucosal infections, including of the upper or lower respiratory tract. The present invention also relates to a method for prophylaxis of an infectious disease in a mammal, comprising administering to said mammal an effective amount of a vaccine comprising in a suitable vehicle a recombinant attenuated Bordetella strain expressing a fusion protein comprising the N-terminal fragment of filamentous haemagglutinin (FHA) and a heterologous epitome or antigenic protein or protein fragment, different from FHA, wherein the gene coding for the native FHA protein is inactivated.

Description

Field of invention: [0001] The present invention relates to novel genetically attenuated strains of Bordetella pertussis expressing a heterologous protein and their use as vaccines, ie for mucosal immunization. [0002] The invention further relates to a method for increasing the immunogenicity of a Bordetella strain. Background of the invention: [0003] Mucosal immunization, such as nasal delivery of the vaccine, has several advantages over classical parenteral vaccination. They are needle-free, less prone to contamination, less dependent on trained medical or paramedical personnel, can induce systemic and mucosal immunity and may be better suited for protection against mucosal infection. [0004] However, most antigens are poor immunogens when delivered nasally and require the addition of effective mucosal adjuvants. One of the most potent mucosal adjuvants is cholera toxin or the closely related E. coli heat-labile enterotoxin and its detoxified derivatives. Unfortuna...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/235C12N1/36
CPCA61K39/12A61K2039/543C07K14/235A61K39/099A61K39/092C12N2760/18534C12N1/36C12N2760/16134A61K2039/523A61K2039/522A61P11/06A61P31/04A61P31/12A61P37/08Y02A50/30
Inventor 卡米尔·洛赫特纳塔利·米耶尔卡雷克哈娜·卡芒
Owner INST NAT DE LA SANTE & DE LA RECHERCHE MEDICALE (INSERM)
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