Structural and functional evolution of broadly neutralizing antibodies against HIV-1
EMSL Project ID
50996
Abstract
The HIV-1 Envelope glycoprotein (Env) mediates entry into host immune cells through a series of receptor-driven conformational changes that lead to fusion of the viral and host membranes. As the sole virally encoded antigen on the surface of HIV-1, Env is also the major target of neutralizing antibodies. Structural characterization of the interactions between broadly neutralizing antibodies (bnAbs) and HIV-1 Env has been pivotal in increasing our understanding of antibody-mediated neutralization of the virus. Much of our understanding of bnAb maturation comes from studies in HIV-1 infected adults that takes years to develop with extensive somatic hypermutation (SHM). Recent data now suggests that HIV-1 infected infants are capable of eliciting a broad response and do so more rapidly than observed in adults. BF520.1 is such an antibody for which we have now isolated two lineage intermediates that represent a pivotal step along the maturation pathway. These intermediate bnAbs have very limited somatic hypermutation and neutralize the majority of HIV-1 isolates neutralized by mature BF520.1. High-resolution characterization of the intermediate bnAbs in complex with Env protein will allow us to determine critical features of the epitope:paratope interactions that enable breadth and potency to be achieved. This information could be instrumental in the design of a germline-targeting immunogens that elicit a similar bnAb response.
Project Details
Start Date
2019-08-01
End Date
2020-01-20
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members