Durable suppression of viremia by lipid nanoparticle-formulated RNA encoding for a highly potent HIV-1 neutralizing antibody
Year: 2026
Type: preprint
Abstract: ABSTRACT Recombinant broadly neutralizing antibodies (bNAbs) are promising tools to treat and prevent HIV-1 infection but are associated with manufacturing challenges. To overcome this limitation, we encoded the potent bNAb 1-18-LS on RNA (1-18-LS RibobNAb) for delivery via lipid nanoparticles (LNPs). Indicating high in vivo antibody expression, a 30 µg RNA-LNP intravenous injection resulted in an average peak 1-18-LS RibobNAb serum concentration of 1,061 µg/mL in human neonatal Fc receptor-transgenic mice. Notably, weekly 30 µg RNA-LNP doses maintained higher trough bNAb levels than 500 µg protein injections. Highlighting potent antiviral activity, RNA-LNP-mediated 1-18-LS RibobNAb monotherapy of viremic HIV-1 YU2 -infected humanized mice resulted in durable HIV-1 suppression without emerging viral escape. Importantly, 1-18-LS RNA-LNP treatment also fully controlled infection after interruption of antiretroviral therapy in humanized mice infected with different patient-derived polyclonal HIV-1 isolates. Our findings provide a proof-of-principle for effective RNA-mediated bNAb immunotherapy of HIV-1 infection.
Authors: Sophie Sayettat, Felix Tolksdorf, Robin Johannson, Johannes Nelke, Alexandra Malz, Leyla Fischer, Imke Gerhard, Nathalie Ullrich, Ursula Ellinghaus, Christiane R. Stadler, Jan P. Bogen, Candice Morin, Jacqueline Knüfer, Ricarda Stumpf, Philipp Schommers, Uğur Şahin, Michael S. Seaman, Sven Kratochvil, Florian Klein, Valentin Le Douce, Henning Gruell
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funder: Deutsche Forschungsgemeinschaft
OpenAlex ID: W7213764045