A good vaccine against HIV comes in threes

Making a vaccine against HIV — the virus that causes AIDS — is sometimes compared to landing on the moon: a number of technical developments were required before the first astronaut was able to walk on the moon. “This all has to do with the virus itself,” says Sanders. “It always knows how to get around the barriers created by scientists in an incredibly smart way.”
But if you look at how quickly vaccines have been developed against COVID, you might ask yourself: why isn’t this possible for HIV? Sanders: “To develop something against COVID is child’s play compared to developing a vaccine to prevent infection with HIV. A few variants are now known of the coronavirus, including the new omicron variant, the first to have a relatively large number of mutations. But HIV variation is many times greater.”
The high number of HIV variants is one of the challenges in the search for a vaccine. With the coronavirus, it was soon possible to find a virus protein that could be put into a vaccine. This protein ensures that the immune system of the vaccinated person produces antibodies against the current SARS-CoV2 variants (although this is not yet clear for the omicron variant). But there are so many different types of HIV around that it is a lot of work to find a protein that triggers an immune response against all variants.

Keeping protein stable

Not only is the search for a suitable protein a challenge, but so is its use in a vaccine. A major obstacle that stood in the way of developing a vaccine against HIV for years was the “instability” of virus proteins. Each time a protein was put into a vaccine, it fell apart. Sanders came up with a trick to keep it stable. “Because of this, we are currently able to test an HIV vaccine with a potentially suitable protein in healthy volunteers at Amsterdam UMC. We are collaborating with Godelieve de Bree of the Department of Internal Medicine to do this. We just finished vaccinating the last of 20 participants.” Sanders’ trick to stabilize this HIV protein turned out to be universally applicable. People worldwide are now benefitting from his method, as it has also been used in the current coronavirus vaccines from Pfizer, Moderna, and Janssen.

Talent scout for B cells

But Sanders knows that even with this discovery, we are not there yet. “We are not going to make it against HIV with just one shot. Multiple vaccines will be necessary, each working in a different way. It starts with activating the right immune cells, the B cells. There are many different B cells, but only some of them can produce the right antibodies against HIV. The first vaccine you give needs to find these B cells. You can think of this vaccine as a talent scout that picks the most promising players from a youth soccer team. In turn, the chosen talents — the B cells — need to learn quite a lot from a youth coach, which is vaccine number two. After that, the head coach starts to work with them, which is the last step: the protein vaccine that teaches the B cells to recognize various strains of HIV.”
Two of these steps are now being investigated by Sander and his team. In addition to the “head coach” vaccine with the stabilized protein, they are also testing a “talent scout” vaccine. This vaccine is being given to another group of healthy volunteers in Amsterdam, New York, and Washington.

Second step

Sanders is not yet able to say anything about the results of both studies, because he does not have enough data. But he wants to emphasize: “If you read or hear that an HIV vaccine study has been successful, you need to realize that it is only one step in a complex story. You really need those other steps as well. And we haven’t fully figured out the second step: the youth coach. We can only take this step after we know the results of the first “talent scout” vaccine.

Original text (in Dutch): Irene van Elzakker
Photo: Martijn Gijsbertsen