It is a pandemic that does not want to end: the AIDS virus HIV (Human Immunodeficiency Virus) can be controlled, but has not yet been defeated. A research team led by Adi Barzel and Alessio Nehmad from Tel Aviv University is trying a new approach: white blood cells – so-called B cells – are genetically modified in such a way that they produce antibodies that attack the virus. Animal experiments on mice have already been successful, and more are now to follow on monkeys. In an interview with ntv.de, Adi Barzel explains what’s behind it.
ntv.de: Herr Barzel, the Polish-French physicist and Nobel Prize winner Marie Curie once said, “You no longer fear what you have learned to understand”. So will the AIDS virus soon be a thing of the past?
It might be a little too early to celebrate. I think it’s a big step forward. Not just in the area of ??AIDS, but in general the ability to manipulate the immune system to fight various diseases.
So not just AIDS?
It doesn’t matter whether it’s infectious diseases, in this case caused by the HI virus, or cancer, autoimmune diseases and allergies – thanks to new technologies, we can meet these challenges better and better. These enable us to manipulate the immune system more effectively. We managed for the first time to develop B cells, a type of white blood cell. This new ability allows us to generate specific antibodies against HIV. We are convinced that these will neutralize the virus, which will prevent the disease AIDS.
How does the HI virus react when it encounters the B cells in the body that you have manipulated?
The virus stimulates the B cells and encourages them to divide, causing the antibodies to spread further. When the virus changes or evolves, the B cells automatically adapt to fight it. With that, we have the first drug that can actually evolve in the patient’s body, which means the virus shouldn’t be able to overcome it.
Over the past two decades, treatments have enabled people living with HIV to live longer. Can your research provide a permanent cure?
We hope so. Our goal is that a single injection should replace the daily drug cocktail that a patient has to take for a lifetime.
How can we imagine such an injection?
At the beginning of our treatment, the patient’s viremia (the virus level in the blood, editor’s note) will be low due to the drug cocktail. The goal of our injection would then be to keep it low and prevent it from rising. We would monitor virus levels for a period after that. Should it rise again, the infected can still return to the cocktail.
If it doesn’t rise again, has the HIV-infected person recovered?
This would be desirable. The formerly infected person should then be able to lead a normal life again, including sexually. HIV patients who are taking antiretroviral therapy in the form of a medicinal cocktail can already do this today. As long as they take the pills, their viraemia is low, so they can have intercourse too.
In recent years, the world has heard a lot about fighting viruses. Is this a breakthrough technology, something that hasn’t been explored yet, at least in relation to HIV?
Yes, it’s groundbreaking, although it’s built on the revolutionary technologies of 2019/2020. We were one of several labs that could develop B cells and now in 2022 we are the first one that can do it in the body. The previous form of this treatment involved extracting B cells from the blood, then treating them in the lab and then reinjecting them. This in turn required sterile rooms and a good manufacturing process. The researchers wore special suits and everything involved a great deal of money and time. With a single injection we want to replace this.
Does this also apply to patients where the AIDS virus has already broken out?
Even patients who are already infected with the AIDS virus and are receiving antiretroviral therapy can live with the disease for many years and do not die immediately from every small infection. With the new treatment method, hopefully without the daily intake of medication.
Could this have a worldwide effect on AIDS?
Scientifically, the answer could be yes. The challenge is of a financial nature, because the drugs involved are expensive. When and how it will reach the less developed countries is an important question. Among other things, foundations like the Bill and Linda Gates Foundation are investing a lot of money, including the research I’m participating in, to bring these drugs to these regions. But there is still a lot of work ahead of us.
What if the successful tests in the animals have little effect on humans?
Of course, despite being related, we are not quite like the monkey. This means that some treatments that have been successful in animal models have failed in humans. But it’s worth a try and we’re learning a lot. With perseverance and patience we will get there in the end.
There are already people taking medication to prevent the risk of HIV infection. How does your research differ from pre-exposure prophylaxis?
Prophylaxis is recommended if you want to avoid infection. After HIV infection, however, it is no longer relevant and millions of infected people need medical treatment. This lasts a lifetime, where patients have to struggle with side effects and must not forget to take it so as not to infect others. That’s why we believe that with just a single injection, relief can be achieved.
When do you think the injection will hit the market?
From my experience, the first human clinical trial can start in five to seven years. Further observation of the individual patients will show whether this vaccination then has to be renewed again and again or lasts a lifetime and what the side effects will be like.
Could a recovered patient become infected with the HI virus again?
The type of antibody we have developed is called a broadly neutralizing antibody. That means it can, at least in theory, defeat many strains of the common HIV virus. Further research would likely lead us to engineer B cells to express more than one antibody, and this combination could neutralize other forms of HIV.
What is CRISPR technology?
Recently, Jennifer Doudna and Emmanuelle Charpentier from the US and France received the Nobel Prize for describing how CRISPR originally served as an immune system against invading viruses. Their findings enabled us to use this system to manipulate human or other cells. These technologies allow us to target a specific location in the genome: the code that tells our cells how to function and our bodies how to grow. It helps us manipulate the genome to change or even destroy a gene there if we don’t want it to be active. Even non-functioning ones can be corrected in this way and even a wish gene can be inserted at a special place in the codex. Thus, the B cells can express the desired antibody incorporated at its specific site due to the activity of the CRISPR.
In your research you work together with scientific centers around the world – for example in the USA. Have you gained international attention in the meantime?
After our research was published in the journal “Nature Biotechnology”, it attracted international attention. I receive many emails from HIV patients around the world who are interested in this treatment. While it will be a few more years before it’s available, the fact that there are, at least in theory, many interested parties is reassuring and hopeful that this injection will help those infected in the near future.
Will this injection affect mankind’s sex life?
This treatment will be expensive and we cannot yet say exactly what side effects it will have. I would recommend everyone to continue to take precautions when having sex and not get infected just because there will be a possible treatment in the years to come. In addition, there are still some other sexual diseases.
Will humanity eventually defeat cancer and Covid-19?
In both diseases, progress is already astounding. The fact that we have Covid-19 vaccines that are very effective is a positive achievement. But more and more is now possible in the treatment of cancer. Of course, it will not be possible to cure every cancer that quickly, but I am optimistic that the constantly new technologies that are being developed will make a difference. Both in reducing suffering and increasing life expectancy.
Tal Leder spoke to Adi Barzel
