Novel Recombinant Bordetella Strains

Abstract

The present invention relates to a genetically attenuated strain of Bordetella pertussis comprising a mutated pertussis toxin (ptx) gene and a heterologous amp G gene and to the presence of filamentous hemagglutinin (FHA ) and a hybrid protein of a heterologous epitope or antigenic protein or protein fragment different from FHA, wherein the gene encoding the native FHA protein is inactivated. The present invention further provides a live attenuated vaccine for the treatment of mucosal or systemic infectious diseases, said live attenuated vaccine comprising a strain of Bordetella pertussis as defined The immune response to a pathogen that infects the upper or lower respiratory tract. The invention also relates to a method for preventing an infectious disease in a mammal, the method comprising administering to said mammal an effective amount of a vaccine comprising a A genetically attenuated strain of Bordetella pertussis comprising a mutated pertussis toxin (ptx) gene and a heterologous amp G gene and directed to N-containing filamentous hemagglutinin (FHA) Expression of a hybrid protein of an end fragment and a heterologous epitope or antigenic protein or protein fragment other than FHA, wherein the gene encoding the native FHA protein is inactivated. The present invention provides a method for enhancing the immune response of a mammal to a pathogen, the method comprising administering a vaccine based on a Bordetella recombinant vector, wherein said Bordetella is resistant to expressing a fusion protein comprising an N-terminal fragment of filamentous hemagglutinin (FHA) and a heterologous epitope or antigenic protein or protein fragment of the pathogen the immune response is sought against, and wherein In the recombinant strain, the gene encoding the native FHA protein was inactivated.

Description

Technical field: [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 technique: [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. Unfortunately, the ...

AI Technical Summary

Problems solved by technology

[0014] In attempting to address the problem of poor immunogenicity obtained with the BPZE1 construct, the inventors have unexpectedly discovered that immunogenicity can be significantly increased when the native fhaB gene encoding the naturally occurring FHA protein is deleted or otherwise inactivated

The present invention therefore solves the problem of a vaccine for mucosal application that is safe and capable of eliciting an effective immunity against an antigen present in a pathogen causing systemic or mucosal infections, including pathogens causing infections of the upper or lower respiratory tract reaction

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