HIV-1 can be neutralized by antibodies which bind to vulnerable structures on the virus surface. One such vulnerable site is the so-called V3 glycan site of the viral envelope protein.
This target structure plays a central role in virus entry into human cells and has therefore long been an important focus for the development of new immunotherapeutic and preventive approaches. However, to date, most identified antibodies have been able to effectively recognize the V3 glycan site only in a subset of HIV variants circulating worldwide.
The newly described antibody, designated 007, targets the V3 glycan site in a different manner than previously known antibodies. Unlike classical V3 antibodies, its binding does not depend on a specific sugar structure that HIV-1 frequently alters to evade the immune response. As a result, in laboratory tests, 007 remains effective against virus variants that are resistant to classical V3 antibodies.
In a mouse model with human immune cells, 007 also effectively enhances existing V3 antibody therapy, forcing the virus to develop multiple changes simultaneously in order to escape. A key finding of the study is that 007 closes existing activity gaps of classical V3 antibodies, and therefore supports antibody therapy combinations that neutralize the virus more effectively.
Vulnerable epitope
“The V3 glycan site has long been considered a vulnerable epitope of HIV-1, but until now it could only be partially exploited therapeutically and for vaccine development,” explains first author Dr Lutz Gieselmann. Dr Malena Rohde, also an author of the study, adds: “The identification of the antibody 007 demonstrates that this weak point can be targeted in a much more versatile way than previously assumed, thereby opening up new perspectives for vaccine development as well.”
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These research findings are therefore of great importance both for the development of new combination therapies and for vaccine development. For use in HIV immunotherapy, 007 has already been licensed exclusively to the company Vir Biotechnology, in partnership with the Gates Foundation in furtherance of its charitable purposes, and is in preclinical development with the support of the Cologne-based start-up Togontech.
This study was supported by the Gates Foundation, the German Research Foundation (DFG), the German Center for Infection Research (DZIF), and the European Research Council (ERC).
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