Shigella as Vaccine-vectors

Bacterial vectors have provided a vaccine technology with broad applicability that could have a significant impact on vaccine development worldwide. The recent development of genetically-defined, attenuated strains of Shigella exhibit many important features of bacterial vectors and are expected to be candidates for novel vaccine vectors. Currently, different attenuated Shigella strains have been developed at Creative Biolabs to enhance the immune response in an effort to generate a safe vaccine platform based on Shigella.

Introduction of Shigella

Shigella as Vaccine-vectors– Creative Biolabs

Shigella is a highly contagious microorganism because as few as 10-100 bacteria can cause Shigellosis (also known as bacillary dysentery), which accounts for high levels of childhood mortality and morbidity. In humans, Shigella specifically invade and colonize the colonic mucosa leading to its disruption. Shigella encompasses four subgroups (S. flexneri, S. sonnei, S. dysenteriae, and S. boydii), each composed of different serotypes, which are identified based on the structure of the lipopolysaccharide O-antigen repeats: Although Shigella is a highly pathogenic microorganism, some attenuated Shigella has been shown to be useful as a vaccine carrier for the delivery of foreign antigens. Among the four Shigella species, S. flexneri is the most frequently isolated species in the world, accounting for 60% of cases in developing countries, and is also the Shigella species most commonly used as a delivery tool.

Why Can Shigella Be Used as Vaccine-vectors?

Several features of the attenuated Shigella make it an attractive vaccine vector: i) it effectively escapes from the endosome and directly enters the cytoplasm host cell, possibly mimicking the vaccine carrier characteristics of Listeria monocytogenes; ii) it naturally targets lymphoid tissue in the colonic mucosa and therefore may elicit mucosal and systemic immune responses against passenger antigens. iii) attenuated Shigella might enter host cells efficiently at sites of induction for mucosal immunity following administration by the oral or intranasal route, without causing significant pathology or disease.

Strategies for Shigella as Vaccine-Vectors

S. flexneri strains are now available that are attenuated and immunogenic in rodents, primates and humans. Creative Biolabs enhances its ability to deliver foreign antigens by modifying the Shigella vector, including mutations or deletions of the gene, such as deletion mutation in the asd gene (Δasd) encoding aspartate p-semialdehyde dehydrogenase, an essential enzyme that is required to synthesize the bacterial cell wall constituent diaminopimelic acid (DAP). We provide mutant strains such as S. flexneri 2a 15D, S. flexneri 2a CVD 1203, S. flexneri 2a SFL124, etc., wherein S. flexneri 2a 15D bears an asd deletion that impairs bacterial cell wall synthesis, resulting in autolysis in the absence of diaminopimelic acid.

Mutant strains of Shigella exhibit many important features of bacterial vectors, including tropism for GALT. However, the most useful feature of bacteria may be the ability to release itself from endosomal vesicles and directly into the host cell cytosol. Creative Biolabs used the ability of Shigella to enter epithelial cells and escape the phagocytic vacuole, developing a method for directing plasmid DNA to the cytoplasm of host cells for protein synthesis and processing for antigen presentation.

The development of new genetic tools has made it possible to develop new and attractive Shigella-based vector vaccines. With an advanced vaccine technology platform and a professional team, Creative Biolabs has developed genetically modified Shigella strains as vaccine vectors to deliver foreign antigens that produce efficient and long-term protection against specific pathogens. If you have any needs, we are your best choice.


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