Salmonella mutant strain capable of efficiently stimulating immune responses and construction method and application of salmonella mutant strain

Abstract

The present invention provides a salmonella mutant strain capable of efficiently stimulating hosts to produce immune responses against shigella flexneri 2a serotype O antigen polysaccharides, and a construction method and an application of the salmonella mutant strain, and belongs to the technical field of bioengineering. The provided salmonella mutant strain has the following gene deletion mutations delta-fliC, delta-fljB, delta-ompA, delta-ompC and delta-ompD, a gene rfbP that is conducive to expression of heterologous O antigen polysaccharides is knocked out, and at the same time, expression plasmids capable of completely expressing the shigella flexneri O antigen polysaccharides are transferred. A preservation number of the salmonella mutant strain is CCTCC NO:M 2020142 and the salmonella mutant strain is preserved in the China Center for Type Culture Collection. By modifying an outer membrane structure of the salmonella, the salmonella mutant strain is more efficient to be used asa polysaccharide presentation carrier. At the same time, the O antigen polysaccharides of the shigella flexneri are expressed in the outer membrane of the salmonella, outer membrane vesicles are purified, the salmonella mutant strain can efficiently stimulate the hosts to produce the immune responses and secrete the outer membrane vesicles, thereby presenting heterologous polysaccharide antigen as a vaccine, and the salmonella mutant strain can be effectively used for prevention and treatment of shigella infection.

Description

technical field [0001] The invention belongs to the technical field of bioengineering, and in particular relates to a Salmonella mutant strain that efficiently stimulates a host to produce an immune response against Shigella O antigen polysaccharide, a construction method and an application. Background technique [0002] Shigella spp. is a highly infectious and pathogenic Gram-negative bacteria that can cause severe diarrhea and even death in humans, commonly known as Shigella, and is the most common cause of human bacillary dysentery. pathogenic bacteria. Dysentery is a kind of enteric infectious disease with high incidence worldwide. According to conservative estimates, the number of infected people in the world exceeds 160 million every year, and the number of deaths exceeds 1.1 million. Dysentery is especially common in developing countries. [0003] Shigella bacteria are divided into four groups. Group A: Shigella dysenteriae (Sh.dysenteriae), commonly known as Shigel...

AI Technical Summary

Problems solved by technology

Existing studies have discovered some potential candidate vaccine targets, among which lipopolysaccharide (Lipopolysaccharide) of Shigella can show better protection, and some studies have proved that the complex of Shigella lipopolysaccharide and protein can stimulate small Rats have a high serum antibody titer and can show a certain degree of protection. Clinical experiments have shown that Shigellaflexneri 2a (Shigellaflexneri 2a) O antigen polysaccharide can cause specific immune protection, but the most critical problem of lipopolysaccharide is to enter the host body , cannot effectively reach the host immune system and be recognized by the immune system, which may lead to immune failure with a certain probability

This defect greatly limits the application effect of Shigella vaccines in actual clinical practice. Therefore, the development of new vaccines is imminent. How to develop new vaccines that can effectively stimulate the host to produce an immune response is an urgent issue. solve

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