Plants might help to prevent the spread of HIV

November 02, 2009 05:13 pm | Updated November 17, 2021 06:38 am IST - Hamburg

People joining red ribbon volunteers during a candle light vigil to pay homage to the people, who lost their lives with HIV infection at a function in Chandigarh. File Photo: Akhilesh Kumar

People joining red ribbon volunteers during a candle light vigil to pay homage to the people, who lost their lives with HIV infection at a function in Chandigarh. File Photo: Akhilesh Kumar

Antibodies that could guard against HIV infection and therefore help to prevent AIDS can now be produced in genetically modified plants, according to a team of German scientists.

The researchers say they have helped to establish the fundamental principles required to produce the HIV-neutralizing antibody 2G12 in genetically modified tobacco plants and are now providing the materials needed for clinical testing.

Every year, about 2.7 million people become infected with HIV.

Antibodies like 2G12 can provide protection against the transmission of the virus by binding to a protein called gp120 which is found on the virus surface. This prevents the virus latching onto its target cells and reduces the chances of infection.

Currently, most antibodies are produced in mammalian cell cultures, a process that is complex and expensive. But the production of antibodies by “molecular farming” in plants is an alternative that costs much less and can be carried out on a much larger scale.

Researchers at the Fraunhofer Institute for Molecular Biology and Applied Ecology (IME) in Aachen, Germany have been instrumental in developing “molecular farming” technology, and in collaboration with 38 industrial and academic partners as part of the European Union’s Pharma-Planta project they have applied this technology in the fight against HIV.

To harvest the antibodies from plants, the scientists first had to isolate the antibody genes from human immune cells and then transfer it to the genome of a tobacco variety known as Petite Havana SR-1.

“The genetically modified plants then produce the antibody protein as they grow,” explains Stephan Hellwig, director of production at the IME.

But how are they able to recover the antibodies from these tobacco plants? To isolate these proteins from several hundred kilos of plant material, the researchers developed an entire process and system for antibody extraction and purification. The harvested tobacco leaves are first washed and crushed, and then the antibodies are extracted and purified in a series of filtration and chromatography steps.

Last year the scientists conducted a pilot test procedure for the first time. After four runs (or “engineering batches“), they processed a total of 800 kilograms of plant material grown in the institute’s own greenhouse.

“In the test runs, we collected the logistical and technical process data that we needed to develop a pilot system which meets the high standards required in the production and purification of pharmacological substances,” explains Juergen Drossard, head of quality assurance at the IME.

“The purified substance was tested in pre-clinical safety studies at the end of 2008 in Britain and no negative effects were observed,” he says.

The German researchers this year built a GMP-compliant, semi-automatic pilot system and commenced operations at Fraunhofer IME. GMP stands for good manufacturing practice and is the very strict regulatory system under which all pharmaceuticals are produced.

Up to 1,000 kilograms of plant material can be processed in the system every week - this being the maximum volume of genetically modified tobacco that the scientists can currently grow in the IME greenhouses.

The pilot system has one particular advantage - the system parts that come into contact with the product are mostly “single-use” disposable components. These disposal components can be replaced easily.

The system can therefore also be used to extract other biopharmaceuticals or secondary metabolites from plants without the risk of cross-contamination or long-lasting change over procedures.

In August the scientists successfully conducted the first test run of the pilot system and performed the first measures required for official regulatory approval of the system.

“Since there are no established, comparable processes, we have to work together with the relevant authorities so that we can ultimately obtain a production permit for a plant-made pharmaceutical that can be used in human beings,” says Drossard, explaining the procedure.

Once the production permit is granted, the scientists are planning to produce the first antibodies under GMP conditions. These will then be used in a Phase I clinical study with one of the EU project partners in Britain.

The German scientists presented their initial findings recently at the Biotechnica 2009 fair in Hanover, Germany.

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