Since 1981, when the disease became known, AIDS has claimed 44 million lives worldwide. It is considered one of the most severe epidemics in human history. Although the number of deaths has decreased over time thanks to education and preventive measures, people still die from the consequences of this disease. During 2024, about 630.000 people died from AIDS worldwide.
Therefore, the discovery of the University Clinic in Cologne raises new hope that it could represent another weapon in the fight against this disease.
More than 800 HIV antibodies tested
The research team led by Florian Klein, director of the Institute of Virology, studied blood samples from 32 people. All of them were infected with HIV, but independently – that is, without therapy – developed a strong and broadly effective immune response through antibodies against the virus.
Scientists tested more than 800 different antibodies from these samples in the laboratory, examining their ability to neutralize HIV viruses. One of them, labeled 04_A06, stood out in particular. This antibody blocks the site where the virus attaches to host cells during infection. In this way, it prevents the HIV virus from entering the cells. Once the virus enters a cell, it takes over its functions and uses it to replicate itself, thereby weakening the immune system in the long term.
The blueprint for antibody production is located in the human immune system – in B-lymphocytes. When they come into contact with pathogens, these lymphocytes mature into plasma cells that produce large quantities of antibodies – among them 04_A06. Researchers have deciphered the genetic blueprint for its creation and managed to reproduce it.
"So, it's no longer necessary to take blood from patients, but that genetic blueprint can be inserted into another cell and told: produce this protein – or rather this antibody."
Antibody 04_A06 – for HIV therapy and prevention
In experiments on mice carrying components of the human immune system and infected with HIV, the 04_A06 antibody was able to completely neutralize most of the HIV virus. The researchers tested about 340 different HIV variants, including those that were already resistant to other antibodies.
"Viruses are very diverse, and that's why HIV is so difficult to treat – because there is a lot of genetic diversity among viruses," Klein explains. The newly discovered antibody, however, was able to neutralize 98 percent of the variants tested.
So 04_A06 could help people who are already infected with HIV, because it prevents the virus from entering the cell. "It binds to the virus's receptor, blocking it and thus preventing it from infecting the target cell." In addition, viruses that are "tagged" with antibodies are more easily recognized and destroyed by the immune system.
This antibody could also be used preventively, to prevent HIV infection: "If the antibody already exists in the body, the virus that enters is immediately stopped before it can infect a cell."
There is no vaccine against HIV yet.
The new antibody could act as a so-called passive immunization. In contrast, active immunization involves a vaccine that allows the body to produce antibodies on its own – but such a vaccine does not yet exist.
There is research into mRNA vaccines, which are designed to stimulate the immune system to respond to a specific protein from the HIV envelope. However, so far this approach has only been tested on one variant of the virus.
Currently, various drugs in tablet or injection form are used for prophylaxis against HIV infection, with great success. However, tablets usually have to be taken daily. Long-acting depot preparations, such as those containing lenacapavir, have already been approved in the US and EU, but are not yet marketed in the EU.
The idea behind antibody prophylaxis like 04_A06, Klein explains, is: “That you can avoid taking a daily pill, because there would be over a 90 percent chance of preventing infection.” Antibody prophylaxis would be taken approximately every six months.
New HIV antibody with high efficacy
Other broadly effective antibodies against HIV have already been discovered, but "04_A06 is definitely an extremely strong representative of that group," says Aleksandra Trkola, director of the Institute of Medical Virology at the University of Zurich.
"Theoretically, 04_A06 alone achieves efficacy that is normally only achieved by combining multiple antibodies."
“Potential” in this context means: even when a small amount of the antibody is applied to infected cells, the effect is very pronounced. This is important if the discovery from Cologne is one day to be turned into a drug that can be administered by injection. Because only a limited amount can be administered – and giving 20 injections would not only be inconvenient, but also very expensive to produce, explains Klein.
The long journey to a cure for AIDS
However, it could be a long time before a real drug based on 04_A06 is developed, says Christoph Spiner, head of the infectious diseases department at the University Clinic "Rechts der Isar" in Munich. He notes that the results from Cologne are currently only laboratory data, "so the effectiveness cannot be directly transferred to real-life conditions." Further studies are needed on the dosage, safety and efficacy of the antibodies.
Aleksandra Trkola also warns: "We still cannot know whether the antibody will prove effective in clinical use." However, she adds: "The signs are certainly very encouraging."
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