24 March 2016

Prevention of HIV infection in situ

GM bacteria of the vaginal microflora will protect against HIV

Roman Fishman, N+1

The California biotech company Osel spoke about the progress in developing a new approach to AIDS prevention based on the use of the natural protective properties of the vaginal microflora. The researchers managed to obtain a GM line of lactobacilli that secrete fragments of antibodies that are able to neutralize the human immunodeficiency virus (HIV) even at the stage of penetration into the body. The authors report these results in the journal AIDS Research and Human Retroviruses (Expression of HIV-1 Neutralizing Antibody Fragments Using Human Vaginal Lactobacillus).

Work on the genetic modification of Lactobacillus Lactobacillus jensenii, typical representatives of the vaginal microflora, has been going on for more than 12 years. Earlier, the head of the research department of Osel, Laurel Lagenaur, and his colleagues have already reported on obtaining GM lines capable of producing cyanovirin-N, a "broad-profile" antiviral protein. The bacteria were successfully tested on macaques, reducing virus transmission by 63%. Now the authors have presented new lines of lactobacilli that secrete antibodies against the viral protein GP120 into the mucosa, which act more specifically.

GP120 protein is considered one of the most important in the HIV envelope: it binds to CD4 receptors on the surface of T-lymphocytes and ensures their infection. This makes GP120 an attractive target for anti-HIV drugs. In particular, it is recognized by small artificially constructed single-domain antibodies m9, m36 and m36.4, the genes of which scientists have introduced into the strain Lactobacillus jensenii-1153. The effectiveness of antibodies expressed by bacteria was demonstrated using the TZM-b cell line (a clone of HeLa cells synthesizing the target of HIV binding – the CD4 membrane protein – as well as carrying the bacterial luciferase gene activated by the HIV promoter).

"Most viruses enter the body through mucous surfaces, and in women, the mucous membranes of the vagina and cervix are the most important gates for HIV," says Laurel Legenaur. – Lactobacilli of the vaginal microflora already play a protective role, weakening inflammatory processes that facilitate the penetration of HIV. The genetic modification of these bacteria will make it possible to obtain antiviral antibodies directly at the site of the invasion."

Osel developers implement these principles in the MucoCept concept, which should be crowned with the widespread medical use of GM lactobacilli capable of preventing the penetration of HIV into the body. According to the company's management, at the moment the technology is only at the development stage, but within two years it will be brought to the stage of clinical trials.

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