The Pharmaceutical Journal
Vol 275 No 7362 p187
13 August 2005

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Genetically modified probiotic could protect against HIV infection

Naturally occurring bacteria that have been genetically modified to protect against HIV infection have been successfully tested in mice, according to US researchers.

They genetically engineered a highly colonising probiotic strain of Escherichia coli (Nissle 1917) so that it secreted HIV-gp41-haemolysin A hybrid peptides, which block HIV fusion and entry into target cells.

The modified bacteria were administered orally or rectally to female mice and the extent of colonisation was determined by bacterial plating assays of the faeces. Some of the mice were given ampicillin, either pretreatment or continuously, to reduce competing microflora. “Although efficient colonisation of mice required antibiotic treatment to reduce competing microflora, colonisation in humans may be more effective because Nissle 1917 is a human, rather than a rodent, strain,” the researchers say.

They discovered that colonisation resulting from either route of administration produced isolates that continued to secrete peptides. Highest concentrations of bacteria were found in the colon and caecum, with lower levels found in the upper intestine, rectum and vagina. The most likely use for genetically engineered Nissle 1917 would be to prevent transmission of HIV during rectal intercourse, say the researchers.

“Although the role of the natural micro-flora in preventing infection by pathogenic microbes is well known, the concept of using genetically engineered organisms for this purpose is a concept that has not been tested in human beings. The severity of the worldwide HIV/AIDS epidemic combined with a lack of effective biomedical interventions warrants such an approach,” they conclude (published online in Proceedings of the National Academy of Sciences on 22 July).