Jun 30, 2022
JERUSALEM WEATHER
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Since acquired immune deficiency syndrome (AIDS) was first discovered over 40 years ago, an estimated 80 million people have been infected with HIV (human immunodeficiency virus) and about 37 million around the world have died of it. It has been the third-deadliest pandemic in world history after the bubonic plague (“Black Death”) in the 14th century and the flu pandemic of 1918 killed up to 50 million people, when the world population was much smaller than it is today. 

The picture shows staining for engineered cells that secrete the antibody against HIV (Photo credit: Tel Aviv University.)

The virus damages the cells in the immune system and weakens one’s ability to fight everyday infections and disease. About 38 million people are living with the disease, thanks to a “cocktail” of pills that they take daily. That development that made the disease much less terrifying than it was before antiretroviral drugs were made available in most countries. There is currently no cure, and we still have a long way to go before a treatment is found that would provide the patients with a permanent cure. But these medications turned AIDS into a chronic disease, making possible a normal life – yet it is still one that can kill if the drugs are unavailable or not taken properly. 

With an early diagnosis and effective treatments, most people with HIV will not develop any AIDS-related illnesses and will live a near-normal lifespan. Most people experience a short flu-like illness two to six weeks after HIV infection, which lasts for a week or two. After these symptoms disappear, HIV may not cause any symptoms for a long time, meaning that many people with HIV don’t know they’re infected, but the virus continues to damage the immune system.

HIV is found in the body fluids of an infected person. This includes semen, vaginal and anal fluids, blood and breast milk. The most common way of getting HIV in is through having anal or vaginal sex without a condom; sharing needles, syringes or other injecting equipment; and transmission from mother to baby during pregnancy, birth or breastfeeding. 

A dramatic and important new study from Tel Aviv University (TAU) and Tel Aviv Sourasky Medical Center, with collaboration from other Israelis and American colleagues, offers a new and unique treatment for AIDS that could be developed into a vaccine or a one-time treatment for HIV patients before they get full-blown AIDS.

In the study the scientists were able, for the first time in the world, to engineer type-B white blood cells in the patient’s body so that they could secrete anti-HIV antibodies. The research used genetic engineering of these blood cells in lab mice so the animals’ bodies could secrete anti-HIV antibodies in response to the virus. 

Alessio Nehmad. (Photo credit: Tel Aviv University.)

The study was led by Dr. Adi Barzel and the doctoral student Alessio Nehmad, both from the school of neurobiology, biochemistry and biophysics at the Wise Faculty of Life Sciences and

Dr. Adi Barzel. (Photo credit: Tel Aviv University.)

the Dotan Center for Advanced Therapies in collaboration with the Sourasky Medical Center. The study was conducted in collaboration with additional researchers from Israel and the US. The study has just been published in the prestigious journal Nature under the title “In vivo engineered B cells secrete high titers of broadly neutralizing anti-HIV antibodies in mice.” 

The lab study was very successful, with all the mice that had been received the treatment responding to the injection and having large quantities in their blood of the antibody that neutralizes HIV. 

One possible way to make HIV halt in its tracks – with a one -ime injection – was developed for the first time in Barzel’s lab. The B-cells the Israeli-led team used are a type of white blood cells responsible for generating antibodies against viruses, bacteria and more. Formed in the bone marrow, they move into the blood and lymphatic system when they mature and from there to the different body parts.

Barzel explained that “until now, only a few scientists – and we among them – had been able to engineer B-cells outside the body. In this study, we were the first to do this in the body and to make these cells generate desired antibodies. The genetic engineering is done with viral carriers derived from viruses that were engineered so as not to cause damage but only to bring the gene coded for the antibody into the B cells in the body. Additionally, in this case, we have been able to accurately introduce the antibodies into a desired site in the B-cell genome. All model animals that had been given the treatment responded and had high quantities of the desired antibody in their blood. We produced the antibody from the blood and made sure it was actually effective in neutralizing the HIV virus in the lab dish.”

The genetic editing was done with CRISPR, a technology based on a bacterial immune system against viruses. The bacteria use the CRISPR systems as a sort of molecular “search engine” to locate viral sequences and cut them so as to disable them. Two biochemists who had figured out the sophisticated defense mechanism – Dr. Emmanuelle Charpentier and Dr. Jennifer Doudna – who became chemistry Nobel Prize winners in 2020 – were able to reroute for the cleavage of any DNA they chose. The technology has since been used to either disable unwanted genes or repair and insert desired genes. 

Doctoral student Alessio Nehmad explained: “We incorporated the capability of a CRISPR to direct the introduction of genes into desired sites along with the capabilities of viral carriers to bring desired genes to desired cells. Thus, we were able to engineer the B-cells inside the body. We use two viral carriers of the AAV family, one carrier codes for the desired antibody and the second carrier codes the CRISPR system. When the CRISPR cuts in the desired site in the genome of the B cells it directs the introduction of the desired gene: the gene coding for the antibody against the HIV virus, which causes AIDS.”

At present, there is no genetic treatment for AIDS, so the research opportunities are huge. Barzel concluded that “we developed an innovative treatment that may defeat the virus with a one-time injection, with the potential of bringing about tremendous improvement in the patients’ condition. When the engineered B-cells encounter the virus, the virus stimulates and encourages them to divide, so we are utilizing the very cause of the disease to combat it. Furthermore, if the virus changes, the B-cells will also change accordingly in order to combat it, so we have created the first medication ever that can evolve in the body and defeat viruses in the ‘arms race.’ ” 

Based on this study, the team said: “We expect that over the coming years, we will be able to produce in this way a medication for AIDS, additional infectious disease and certain types of cancer caused by a virus, such as cervical cancer, head and neck cancer and more.”