Scouting, training and polishing: in search of a world-class HIV vaccine

There is not yet a vaccine against the second deadliest infection in the world after tuberculosis: HIV. No one has been able to develop a vaccine thus far, but Professor of Virology Rogier Sanders of Amsterdam UMC is optimistic about the possibility of developing one now, specifically targeting rare immune cells capable of making antibodies. Funding is coming from the Bill & Melinda Gates Foundation. 

 There are an estimated 40 million people worldwide living with HIV, the virus that causes AIDS. Two-thirds of this group lives on the African continent. In 2022, more than 600,000 people died from HIV-related causes and more than 1.3 million people became infected. There is not yet a vaccine against the second deadliest infection in the world after tuberculosis. Professor of Virology Rogier Sanders of Amsterdam UMC is positive about the possibility of developing a vaccine, with financial support from the Bill & Melinda Gates Foundation. 

 “We hope to develop a preventive vaccine by designing and testing immunogens that generate neutralizing antibodies against HIV. So far, no one has succeeded in doing this,” says Sanders. However, according to Sanders, there are reasons to be positive. “There is a lot of optimism in the HIV vaccine research world right now. There are quite a few positive results from several early-stage studies of experimental vaccines that elicit an immune response against a wide range of HIV variants,” Sanders explains. “All the vaccines that have failed so far have not been able to induce neutralizing antibodies, let alone broadly neutralizing antibodies. But very good progress has been made in the meantime.”  

Building on progress  

Sanders’ team, which includes researchers from Stanford University, Weill Cornell Medical College and the University of Louisiana, wants to build on this “great progress” by developing a vaccine that specifically targets rare immune cells capable of making antibodies that neutralize the virus. This process, known as ‘Germline Targeting’, guides the immune system to produce antibodies that respond to HIV infection. A study recently published in Science has already shown that this process works.  

Strong defenders  

The next step is to develop ways to stimulate the immune response through a process known as ‘priming, shaping and polishing’. In doing so, the immune cells follow a developmental path to become stronger defenders. “Think of human immune cells as a youth football team. First, the vaccine scouts and recruits the talents from this youth team, and once the right cells have been primed (priming), and gone through multiple training phases (shaping), the talented players are then polished. ) to world-class football players,” says Sanders. This process could ultimately lead to an immune response that is strong enough to ward off an HIV infection and therefore to a fully functioning vaccine.  

Unusual properties  

Although this sounds simple, the hunt for an HIV vaccine has presented virologists with many conundrums. There has still not been a successful phase III study involving a large group of subjects since the 1980s. This is mainly due to the unusual properties of HIV. “There are so many things to take into account,” Sanders explains. “There are a number of reasons why it is so difficult to make a vaccine and one of them is the diversity of the virus. A second difficulty lies in the structural or chemical properties of the protein surrounding the virus, which is crucial for vaccines.” Sanders’ team recently took an important step with a ‘priming’ vaccine that was tested in a phase I study in test subjects in New York, Washington and Amsterdam (at Amsterdam UMC). “We are hopeful that we will eventually succeed in developing an effective vaccine against the many variants of HIV. Hopefully that will put an end to the ongoing misery caused by the virus,” Sanders said.  

With the €4.5 million grant from the Gates Foundation, Sanders and his team hope to achieve their goals within 5 years. IXA is closely involved regarding patents, licensing and developing the business case.