Antibody response against Escherichia coli heat-stable enterotoxin expressed as fusions to flagellin

Antibody response against Escherichia coli heat-stable enterotoxin expressed as fusions to flagellin

Author Pereira, Catia Mendes Autor UNIFESP Google Scholar
Guth, Beatriz Ernestina Cabilio Autor UNIFESP Google Scholar
Sbrogio-Almeida, Maria Elisabete Google Scholar
Castilho, Beatriz Amaral da Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Inst Butantan
Abstract The heat-stable toxin (ST) produced by enterotoxigenic Escherichia coli strains causes diarrhoea by altering the fluid secretion in intestinal epithelial cells. Here, the effectiveness of a flagellin fusion protein of Salmonella containing a 19-amino-acid sequence derived from the ST sequence (FLA-ST) in generating antibodies capable of neutralizing the toxic activity of ST was evaluated. This fusion protein, and an alternative construction where two cysteine residues in the ST sequence were substituted by alanines (ST,), were delivered to the immune system by three distinct strategies: (i) orally, using an attenuated Salmonella strain expressing FLA-ST; (ii) intraperitoneally, by injection of purified FLA-ST; (iii) orally, using attenuated Salmonella carrying a eukaryotic expression plasmid (pCDNA3) with the gene encoding FLA-ST. The results showed that the flagellin system can be used as a carrier to generate ST-neutralizing antibodies. However, it should be mentioned that humoral immune response against ST was only obtained when the mutated ST sequence was employed. FLA-ST was found to be non-immunogenic when delivered via the oral route with attenuated Salmonella strains. However, a flagellin antibody response was obtained by immunizing mice with Salmonella carrying pCDNA3/FLA-STmt. Oral immunization with Salmonella carrying the eukaryotic expression plasmid (pCDNA3/FLA-STmt) seems to be a promising method to elicit an appropriate response against fusions to flagellin.
Keywords ETEC
attenuated Salmonella
flagellin fusions
mucosal vaccines
Language English
Date 2001-04-01
Published in Microbiology-uk. Reading: Soc General Microbiology, v. 147, n. 4, p. 861-867, 2001.
ISSN 1350-0872 (Sherpa/Romeo, impact factor)
Publisher Soc General Microbiology
Extent 861-867
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000168105000010

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