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Single-Chain Variable Fragments of Broadly Neutralizing Antibodies Prevent HIV Cell-Cell Transmission

Year: 2021

Type: article

Abstract: Broadly neutralizing antibodies (bNAbs) are a major focus for passive immunization against HIV, with the recently concluded HVTN Antibody Mediated Protection trial providing proof of concept. Most studies focus on cell-free HIV; however, cell-associated virus may play a significant role in HIV infection, pathogenesis, and latency. Single-chain variable fragments (scFv) of antibodies may have increased tissue penetration and reduced immunogenicity. We previously demonstrated that scFv of four HIV-directed bNAbs (CAP256.25, PGT121, 3BNC117, and 10E8v4) retain significant potency and breadth against cell-free HIV. As some bNAbs have been shown to lose potency against cell-associated virus, we investigated the ability of bNAb scFv to neutralize this mode of transmission. We demonstrate that unlike IgG, scFv of bNAbs are able to neutralize cell-free and cell-associated virus with similar potency. These scFv, which show functional activity in the therapeutic range, may therefore be suitable for further development as passive immunity for HIV prevention.

Source: Journal of Virology

DOI: 10.1128/jvi.01934-21

Authors: Rebecca T. van Dorsten, Lucia Reh, Alexandra Trkola, Lynn Morris, Penny L. Moore