Tag: lenacapavir

Worldwide, 44 million deaths — that is the sad toll of HIV/AIDS since it was first detected in 1981; it was officially discovered in 1983. AIDS is considered one of the worst epidemics in human history.

The number of AIDS-related deaths has steadily decreased over the years, thanks to awareness campaigns, education and prevention, but people are still dying.

In 2024, UNAIDS reported the number of AIDS-related deaths a year was about 630,000 people worldwide.

The new discovery of an antibody against HIV by the University Hospital of Cologne, Germany, has raised hopes that another weapon in the fight against the virus may be on the horizon.

More than 800 antibodies tested against HIV

The research team, led by Florian Klein, Director of the Institute of Virology in Cologne, examined blood samples from 32 people. They were all infected with HIV, but had developed a particularly strong and broadly effective antibody response against the virus, on their own — without any medical intervention.

The researchers tested more than 800 different antibodies from these blood samples for their ability to neutralize HIV.

One of them, named 04_A06, stood out. The antibody blocks a site where the virus binds to cells when it infects a person. It therefore prevents HIV from entering the body’s cells. When the virus enters a cell, it reprograms the cell to reproduce the virus, and that weakens the immune system in the long-term.

Antibodies in the human immune system are produced by B lymphocytes, or B cells.

When B cells detect pathogens, they become plasma cells that release antibodies, such as the 04_A06 antibody discovered by the Cologne researchers.

The researchers decoded this process, or “blueprint,” for the 04_A06 antibody in the hope that they could reproduced it.

“You use the genetic blueprint of the antibody, transfer it to a cell line in the laboratory and use another cell and tell it: Please produce this antibody,” Klein told DW.

Antibody 04_A06: HIV treatment and prevention

In experiments with mice that had been infected with HIV, the 04_A06 antibody was seen to neutralize most HIV infections.

In total, the researchers ran experiments with almost 340 variants of HIV, including those that were resistant to other antibodies.

“HIV has a high genetic diversity, the viruses are all quite different,” said Klein. “That’s what makes HIV so difficult to treat.”

But the 04_A06 antibody neutralized 98% of the HIV variants they tested.

The researchers said the 04_A06 antibody may be able to help people who are already infected with HIV — because it blocks the virus’ access to cells.

“It attaches itself to the envelope protein of the virus, so the virus can no longer infect the target cell,” said Klein. In addition, viruses blocked by 04_A06 were better recognized and actively eliminated by the body’s immune system.

The researchers hope that 04_A06 could also prevent HIV infections.

“The antibody intercepts viruses before they can infect cells and multiply in the body,” said Klein.

So, the newly discovered antibody could act as a passive immunization. An active immunization would be a vaccine that enables the body to produce antibodies itself. But there is no HIV vaccine as yet.

The state of HIV vaccine development and medication

Studies into an HIV vaccine based on mRNA technology are ongoing. Researchers aim to stimulate an immune response with a protein taken from the HIV envelope. That is the virus’ outer coat, which, like the one of the virus that causes COVID-19, has protein spikes embedded in it that enable the virus to attach itself to cells and infect them. However, this method has so far only been tested for one HIV variant.

Klein said it will be a challenge to induce the body’s own production of potent and broadly neutralizing antibodies with an active vaccine.

Various medicines are offered as pills or injections as a prophylactic measure against HIV infection. And they are very successful. However, the tablets usually have to be taken daily.

There are long-acting, injectable prophylaxis drugs, such as lenacapavir or cabotegravir, that create a “depot” function in the body. The depot allows the body to release the active ingredient slowly. And that means you only need two injections per year.

Klein said the idea behind antibody prophylaxis with 04_A06 was, “that you [could] do without tablets, because you would have a more than 90% chance of preventing an infection.” An antibody prophylaxis using 04_A06 would have to be taken approximately every six months, much like lenacapavir.

Alternatives to the 04_A06 antibody

Researchers have found other broadly neutralizing antibodies against HIV.

However, Alexandra Trkola, Director of the Institute of Medical Virology at the University of Zurich said, “04_A06 is definitely an extraordinarily potent representative of this group.”

The antibody’s potency determines how many — or how few — of the antibodies are needed to create a strong effect. This is important if the Cologne discovery is to become a drug that is administered by injection, for example.

Potency also determines how often you would need an injection.

“Theoretically, 04_A06 alone achieves an efficacy that is otherwise only achieved in antibody combinations,” said Trkola, who was not part of the research in Cologne.

But it will probably be a while before 04_A06 becomes a drug, said Christoph Spinner, Head of Infectiology at the Klinikum rechts der Isar at the Technical University of Munich (TUM).

The Cologne study has so far only involved laboratory data, said Spinner, who was also not involved in the research. “So, the effectiveness cannot be directly transferred to real life.”

Further studies on the dosage, people’s tolerance to it and its efficacy would need to follow, he said.

Trkola agreed it was not yet possible to predict whether the antibody would prove its efficacy in clinical use but added that the signs were “definitely promising.”

(DW)