Biophysical Imaging

The Env glycoprotein is the only viral protein exposed on the HIV-1 surface and thus, constitutes a prime target in the antiviral immune response. Most antibodies targeting Env offer protection against a limited number of HIV strains, but a few that recognise the conserved MPER region in Env show a nearly pan-neutralising capacity. The exceptional antiviral activity of anti-MPER antibodies heavily relies on their ability to interact with the viral membrane, although the contribution of this process to the neutralisation breadth and potency is poorly understood. In this work we have investigated the nature of antibody-Env and antibody-membrane interactions using super-resolution STED microscopy and fluorescence correlation spectroscopy. We have found that anti-MPER antibodies 10E8 and 4E10 do not spontaneously bind the viral membrane, but use lipid-interacting regions as secondary docking sites to increase affinity for the Env glycoprotein. MD simulations support the conclusion that bulk biophysical membrane properties govern antibody dynamics. Notably, we have engineered lipid interaction sites in antibodies to enhance their neutralising activity. Overall, this work shows how biophysical characterisations of antibodypathogen interactions can contribute to the development of innovative antiviral strategies.