Bordetella pertussis as Vaccine-vectors

Bordetella pertussis (B. pertussis), the causative agent of whooping cough, is a promising and attractive candidate for vaccine delivery via the nasal route. The detailed understanding of the molecular mechanisms of B. pertussis virulence has led to the design of attenuated B. pertussis strains, which are sufficiently safe to be considered as live recombinant vaccine vectors to deliver the antigen to the immune system. Creative Biolabs is a world leader in the field of vaccines vector design. With our extensive experience and professional team, we are therefore confident in offering the best bacterial vaccine vector design services.

Bordetella pertussis as Vaccine-vectors– Creative Biolabs

Introduction of Bordetella pertussis

Bordetella pertussis, a Gram-negative bacterium, is the causative agent of pertussis or whooping cough. B. pertussis establishes infection in the upper respiratory tract by producing many virulence factors, including adhesins and toxins. It colonizes the human respiratory tract very efficiently and induces strong and protective local and systemic immune responses after a single nasal administration, even in distal mucosal sites, such as the urogenital tract. Consequently, B. pertussis has been successfully used as a live bacterial vector for the presentation of foreign antigens to the respiratory mucosa.

Why Can Bordetella pertussis Be Used as a Vaccine Carrier?

The potential of B. pertussis as a nasal vaccine delivery vehicle lies in its ability to efficiently colonize the human respiratory tract and induce local and systemic immune responses. It can be easily genetically manipulated through a variety of genetic tools. In addition, the completion of the Bordetella genome sequencing project has allowed for an in-depth study of the pathogenesis of B. pertussis. Importantly, the microorganism expresses various protein secretion systems which allow secretion and/or exposure of foreign antigens on the bacterial surface. Last but not least, B. pertussis is known and used for its adjuvant properties, thus further supporting the development of this bacterium as a live recombinant vaccine vector.

Our Strategies for Bordetella pertussis as Vaccine-vectors

Strains

  • The attenuated B. pertussis strain BPRA lacks the gene encoding pertussis toxin but retains the ability to colonize the respiratory tract as effectively as the parental strain, and a single dose provides full protection against subsequent challenge with virulent B. pertussis.
  • BPZE1, which deleted for the dermonecrotic (DNT)-encoding gene, produces an enzymatically inactive pertussis toxin (iPTX) and overexpresses E. coli ampG gene to reduce tracheal cytotoxin (TCT) release in the extracellular milieu. The BPZE1 strain still remains the ability to colonize the lungs efficiently and induce protective immunity against pertussis infection.

Filamentous hemagglutinin

The exogenous gene is introduced into the chromosome by insertion into the fhaB gene, which encodes filamentous hemagglutinin (FHA). FHA, an important protective antigen, is a major surface-associated and secreted protein of B. pertussis and it also appears to have immunomodulatory properties. The fusion to FHA allows surface presentation and secretion of the fused passenger antigen.

BrkA-based autotransporter

Autotransporters are large, secreted, usually virulence-associated proteins of Gram-negative bacteria. BrkA, an autotransporter protein expressed in B. pertussis, confers serum resistance by inhibiting the classical pathway of complement activation and plays a role in B. pertussis adhesion and invasion of the host cells. It is expressed as a 103-kDa precursor and is processed during secretion to produce a 73 kDa N-terminal passenger domain and a 30-kDa C-terminal translocation unit. After translocation, the cleaved passenger domain is closely related to the bacterial surface. Fusion of the antigen to BrkA or its truncated version with a large deletion within its passenger domain can present the foreign antigen on the surface of the bacteria.

Adenylate cyclase toxin

Adenylate cyclase toxin (CyaA) is one of the major virulence factors of B. pertussis, and is involved in bacterial colonization of the airways and development of whooping cough. The CyaA toxin is a 1,706-residue bifunctional protein: the catalytic domain is located at the 400 amino-terminal residues, while the carboxy-terminal 1,306-residue is associated with the toxin-binding cellular receptor. There are four different sites in the ACT catalytic domain for insertion of heterologous antigens, which allows expression of multiple antigens in a single ACT protein. These properties have been utilized to design CyaA toxins as potent non-replicating vectors capable of delivering antigens into antigen presenting cells and eliciting specific cell-mediated immune responses.

B. pertussis represents an appealing platform for the development of live recombinant vaccines delivered via the nasal route that would confer simultaneous protection against pertussis and the targeted infectious diseases. With years of experience and advanced vaccine technology platform, Creative Biolabs offers a variety of vaccine vector design services based on B. pertussis. If you are interested in our services, please feel free to contact us.


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