Afucosylated broadly neutralising antibodies targeting HIV envelope elicit enhanced NK cell-mediated cytotoxicity against HIV-infected CD4+ T cell and macrophage targets.

• Tác giả: Morgane M Brunton-O'Sullivan, Amy W Chung, Anna C Hearps, Anthony Jaworowski, Christine Jordan, Hans Kek, Pantelis Poumbourios, Pradhipa Ramanathan, Laura Rikard-Bell, Olivia Wilhelm, Bruce D Wines
• Ngôn ngữ: eng
• Thông tin xuất bản: England : Journal of leukocyte biology , 2025
• Bộ sưu tập: NCBI
• ID: 708635

Tóm tắt

Enhancement of antibody-dependent cellular cytotoxicity (ADCC) is a promising adjunct approach to achieve HIV control in the absence of antiretroviral therapy but requires the development of potent ADCC-eliciting antibodies which can recognise diverse HIV-infected cell types. A panel of broadly neutralising antibodies (bNAbs) targeting HIV envelope were identified which specifically bind both HIV-infected CD4+ T cells and monocyte-derived macrophages (MDM). Afucosylated versions of these bNAbs containing ≈30% less core fucose were generated and elicited a significant increase in ADCC responses from NK cells against HIV-infected T cell and MDM targets. Afucosylation did not alter virus neutralisation or cell-binding activity of these bNAbs. Afucosylation modifications of bNAb Fc regions is thus a promising strategy to enhance Fc-mediated activity against both T cell and macrophage targets in vivo which may be employed to heighten the therapeutic potential of antibody-based immunotherapy approaches for drug-free HIV control.