Vibrio Cholerae as Vaccine-vectors

Vibrio cholerae as a carrier organism capable of expressing heterologous antigens on the mucosal surface is an attractive tool for the development of novel vaccines. Creative Biolabs has been working on new vaccine vectors for many years and providing Vibrio cholerae vaccine vector design services to customers worldwide. As a service provider, our goal is to provide the highest level of service, confidentiality, and customer support.

Introduction of Vibrio Cholerae

Vibrio cholerae (V. cholerae), is the etiologic agent of cholera, a devastating diarrheal disease which causes epidemics and pandemics. V. cholerae is a Gram-negative, non-spore forming curved rod that was found in diverse aquatic ecosystems around the planet. The bacterial strains are classified into more than 200 serogroups based on the surface O antigens. Only O1 and O139 serogroups have inherent cholera epidemic/pandemic potential while those of non-O1/non-O139 serogroups cause merely sporadic infection such as gastroenteritis and/or septicemia. The V. cholerae O1 strain is further divided into two biotypes named El Tor and classical, on the basis of biochemical differences and bacteriophage susceptibility.

Characteristics of Vibrio Cholerae as Delivery Vehicle

As a delivery tool, V. cholerae has the following features: i) V. cholerae is a non-invasive organism that effectively colonizes the human intestinal mucosa and induces a long-lasting immune response; ii) live, attenuated V. cholerae vaccine strains can be administered orally, and these strains have been well characterized and shown to be safe and immunogenic to humans; iii) the V. cholerae vaccine strain can secrete immunoadjuvant in vivo, such as the LT (R192G), a non-toxic mutant of Escherichia coli heat labile enterotoxin, and can express large quantities of heterologous antigens in a balanced lethal plasmid expression system; iv) V. cholerae can also efficiently express and secrete both large and small heterologous antigens, and mouse models of V. cholerae infection have been developed which allow rapid preliminary assessment of V. cholerae vaccine and vector strains in vivo.

Our Strategies of Vibrio Cholerae as Vaccine-vectors

• Strains

All recently developed live oral cholera vaccine strains have deletions in the genes encoding the subunits of cholera toxin, which is the most important virulence factor for V. cholerae in producing diarrhea. Live attenuated vector strains of V. cholerae were derived from Peru-2, a Peruvian El Tor Inaba strain deleted for the cholera toxin genetic element and attRS1 sequences, which was developed as a live, oral vaccine strain.

• Promoters

By evaluating the activities of many promoters in vitro and in vivo, Creative Biolabs has provided optimal promoters for the expression of heterologous antigens under specific conditions by vaccines and vector strains of V. cholerae, such as the heat shock htpG promoter (induced under conditions of environmental stress) and the V. cholerae iron-regulated irgA promoter (induced under low-iron conditions).

• Balanced Lethal System

The glutamine synthetase encoded by glnA is an enzyme necessary for the synthesis of glutamine and is responsible for the assimilation of ammonia when the extracellular nitrogen concentration is low. Creative Biolabs developed the V. cholera vaccine strain Peru2ΔglnA, which is derived from Peru2 and deficient in glutamine synthetase. This strain cannot grow on M9 minimal medium lacking glutamine, but this growth deficiency is complemented by the plasmid containing a complete copy of the Salmonella typhimurium glnA gene. This balanced lethal system that allows the construction and maintenance of V. cholerae vaccine and vector strains that express high levels of immunogenic antigen from plasmid vectors without the need for antibiotic selection pressure.

Vibrio cholerae has a number of attributes that make it an attractive candidate for use as a vaccine vector for inducing mucosal immunity against heterologous antigens. With years of experience and advanced vaccine technology platform, Creative Biolabs has developed engineered and attenuated V. cholerae vectors that deliver proteins in vitro and in vivo. If you have any need for V. cholerae as a delivery vehicle, we are your best choice.

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