Shigella dysenteriae Vaccines

Focusing on the development of various vaccines, it is the mission of Creative Biolabs to continuously deliver the highest quality and reliable products and services to researchers around the world. In the more than ten years of growth, we have gradually established a comprehensive and systematic research and development system and built a scientific and perfect product and service layout. We have a team of experts who are well versed in all kinds of vaccine research. Especially in the case of bacterial vaccines, we are able to design, prepare and evaluate various specific bacterial vaccines and provide the most comprehensive and reliable products to meet your needs for vaccine research.

Shigella dysenteriae

Shigella dysenteriae is a Gram-negative rod-shaped bacterium that does not produce spores and survives both anaerobic and aerobic conditions. The surface of S. dysenteriae contains fimbriae of 1-2 μm in length and is responsible for the attachment of the cells to the host. S. dysenteriae can cause acute intestinal disease - Shigellosis. The disease is a diarrhea caused by Shigella, which is characterized by watery diarrhea in the early stages of the disease, followed by typical dysentery-like stools, small in size and bloody. S. dysenteriae is able to invade intestinal epithelial cells and replicate within the cells, eventually destroying the cells and causing diarrhea. Only humans and non-human primates can carry the bacterium. Bacteria spread between people through the fecal-oral route. Sexually, in direct contact, and through contaminated water and food can cause disease. The bacteria are highly infectious and require only 10 microorganisms to cause disease.

Pathogenicity of Shigella dysenteriae

According to the O antigen in lipopolysaccharide, Shigella can be divided into four types: S. dysenteriae, S. flexneri, S. Boydii, and S. sonnei. Among them, S. dysenteriae is the main cause of fatal diarrhea in less developed countries. The pathogenicity of S. dysenteriae is based on its ability to invade and colonize human intestinal epithelial cells. Under the infiltration of polynuclear leukocytes, bacteria can trigger a strong acute inflammatory response. The ability of S. dysenteriae to pass through the colonic mucosa through M cells determines the pathogenicity of the bacteria. The virulence factors associated with bacterial invasion of epithelial cells are encoded by a plasmid different from enteroinvasive E. coli (EIEC) and virulent Shigella. Shiga toxin is the most important virulence factor of S. dysenteriae, which inhibits protein synthesis, induces bloody diarrhea, causes hemolytic uremic syndrome, and hemorrhagic colitis. The Shiga toxin is composed of 5 B subunits and 1 A subunit, wherein the A subunit has enzymatic activity, which can irreversibly inactivate the host ribosome, thereby terminating the host protein synthesis. The action of the A subunit begins with the binding of the B subunits to the host surface receptor, the toxin is taken up into the cytoplasm by the host, and the A subunit is separated from the B subunits.

Bacterial invasion of epithelial cells is multi-step. First, the bacteria invade the M cells in the gastrointestinal epithelial cells, which then transport the bacterial antigens to the macrophages in the underlying tissue. Macrophages, upon exposure to S. dysenteriae, initiate an apoptotic program and release the inflammatory cytokine IL-1. It is the IpaB protein of S. dysenteriae, which activates macrophage apoptosis and activates pro-IL-1 into IL-1. After lysing the macrophages, the bacteria can reach the basolateral side of the epithelial cells and enter the epithelial cells by endocytosis. The Type III secretion system of bacteria (T3SS) is an important virulence element for its entry into cells. The chain reaction of bacteria in the cell promotes their spread, and the aggregated Arp2/3 complex in this process ensures that the bacteria travel from one cell to another. At the same time, bacteria that remain in the cell can avoid the humoral immune response of the host and the effects of extracellular toxins.

Development of the Shigella dysenteriae Vaccines

The two most promising ways to prepare Shigella vaccines are live attenuated strains and non-cellular vaccines based on lipopolysaccharide or polysaccharide antigens. The use of genetic modification methods to increase exposure of common outer membrane proteins is likely to be an effective method for preparing universal Shigella vaccines. WRSd1 was deleted from S. dysenteriae 1 strain 1617 by a virG gene associated with intracellular transmission of bacteria and a sequence containing the Shiga toxin gene. The vaccine showed good protection on the guinea pig model. At the same time, the combination of the vaccine with WRSS1 (Shigella. sonnei vaccine strain) and SC602 (Shigella. flexneri 2a vaccine strain) showed that the vaccine mixture can protect the test animals from the challenge of the three homologous strains, but compared to WRSS1 and SC602, WRSd1 has a lower level of protection in combination vaccines than when immunized alone. A hexavalent heat-inactivated vaccine developed by India containing S. dysenteriae, S. sonnei, S. flexneri 2a, S. flexneri 3a, S. flexneri 6 has been shown to have good results in guinea pig models. It is immunogenic and capable of producing protection against heterologous challenges. In addition, the fusion protein DB Fusion, which fuses two Type III secretion system antigens, Ipa B (invasion plasmid antigen B) and Ipa D (invasion plasmid antigen D), and a 34 kDa conserved protein from Shigella flexneri 2a MOMP (major outer membrane protein)-34 kDa OmpA showed protection in animal experiments.

Creative Biolabs is an international vaccine research and services company with a high level of expertise that enables us to help vaccine researchers around the world to solve their problems in R&D and to win high praise. In the field of bacterial vaccines, we are also at the forefront of the world. Regardless of any questions you have about vaccine development, please contact us and we will definitely solve your problem.


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