Escherichia coli heat-labile enterotoxin gene fragment and application thereof

Abstract

The invention discloses an escherichia coli heat-labile enterotoxin gene fragment, a fusion gene and applications thereof. A nucleotide sequence of the escherichia coli heat-labile enterotoxin (LT) gene is shown in Seq ID No.1. The gene fragment is a gene fragment after removing any contiguous fragments within 100-585 bp of an encoding nucleotide sequence of an LA A subunit gene. The fusion gene includes the escherichia coli heat-labile enterotoxin gene fragment and a gene fragment rich in antigen epitopes of a pathogenic microorganism. A gene fragment of a candidate antigen is inserted into the LT A1 gene fragment and replaces a toxic site as a vaccine antigen. Through the connection between an A2 fragment and an LTB, a mucosal adjuvant structural basis and activity of the LT are retained, and he toxicity is removed. Mucosal immune response of a body can be effectively induced by mucosal immunization so as to produce specific IgA antibodies. Therefore, a vaccine method for prevent pathogenic microorganisms from infecting through a mucosal route is provided. Moreover, no report on the aspect appears at present.

Description

technical field [0001] The invention relates to biopharmaceuticals, in particular to Escherichia coli heat-labile enterotoxin gene fragments and applications thereof. Background technique [0002] The vast majority of infections occur or originate from mucosal surfaces. These typical infections include: (1) Common microorganisms in gastrointestinal tract infections: Helicobacter pylori, Vibrio cholerae, pathogenic Escherichia coli, Campylobacter jejuni, Salmonella, Chi Shigella, rotavirus, poliovirus, etc. (2) Common microorganisms in respiratory tract infection: Mycoplasma pneumoniae, respiratory syncytial virus, influenza virus, etc. (3) Common microorganisms in genitourinary system infection: HIV, Chlamydia, Neisseria gonorrhoeae, herpes simplex virus, certain strains of pathogenic Escherichia coli, etc. These microorganisms are still a serious threat to human health and a great challenge to the development of vaccines. A large number of studies have shown that the sys...

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Problems solved by technology

LTK63 (mutation of serine at position 63 of the LTA subunit to lysine) has little LT toxicity, and LTR72 (mutation of alanine at position 72 of the LTA subunit to arginine) has strong mucosal adjuvant properties, but its retention is large ADP-ribosyltransferase toxicity, LTR192G (LTA subunit 192 arginine mutated to glycine) has been used as a mucosal adjuvant in human trials, resulting in a strong immune response, but it cannot eradicate the existing bacterial infection , and several volunteers developed diarrhea[Park EJ, Chang JH, Kim JS, et al. 2):72-78]

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