Assessing bnAb potency in the context of HIV-1 envelope conformational plasticity
Scientists around the world are working to develop vaccines and treatments for HIV that rely on special antibodies called broadly neutralizing antibodies (bnAbs). These antibodies can target and block a wide variety of HIV strains. However, one of the big challenges in HIV research is that the virus constantly changes shape, making it harder for antibodies to bind and stop it.
In a recent study, Caio Foulkes and Alexandra Trkola explored how changes in the shape of the HIV envelope—the outer shell of the virus—affect how well these powerful antibodies can work. This envelope is very flexible, and the virus can “hide” its most vulnerable parts by keeping the envelope in a tightly closed form. But sometimes, the virus opens up, exposing these regions.
To study this, the team created a panel of 19 HIV variants (called “SENSE-19”) with specific mutations that caused the virus envelope to become more open. They then tested how well different antibodies worked against these variants. What they found was surprising: not all antibodies react the same way. Some became more effective against open versions of the virus, while others became less effective.
Importantly, the study found that certain bnAbs—especially those targeting a part of the virus called the MPER region—worked better when the virus envelope was open. Others, like those targeting the CD4 binding site, maintained strong performance even when the virus changed shape. This suggests that some antibodies are more “tolerant” of the virus’s shape-shifting than others.
The findings help explain why some antibodies are more reliable than others across different HIV strains. This knowledge is critical for designing vaccines that aim to trigger only the most effective antibodies. The Swiss HIV Cohort Study (SHCS) played a vital role in supporting this research. SHCS provided funding and biological samples from people living with HIV, enabling scientists to test real-world virus-antibody interactions. Their contribution continues to be essential in advancing HIV science.
This research brings scientists one step closer to developing vaccines and antibody-based therapies that can outsmart HIV’s tricks and protect people worldwide.