Durable suppression of viremia by lipid nanoparticle-formulated RNA encoding for a highly potent HIV-1 neutralizing antibody
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 ug RNA-LNP intravenous injection resulted in an average…
A groundbreaking study has demonstrated the potential of lipid nanoparticle-formulated RNA to effectively suppress HIV-1 infection. The research focused on encoding the highly potent HIV-1 neutralizing antibody, 1-18-LS, on RNA, which was then delivered via lipid nanoparticles (LNPs).
Human neonatal Fc receptor-transgenic mice injected with 30 micrograms of RNA-LNP saw an average peak serum concentration of 1,061 micrograms per milliliter of the 1-18-LS RibobNAb. Remarkably, weekly 30 microgram RNA-LNP doses maintained higher trough levels of the bNAb compared to 500 microgram protein injections.
The study found that RNA-LNP-mediated 1-18-LS RibobNAb monotherapy in HIV-1YU2-infected humanized mice led to durable HIV-1 suppression without any emerging viral escape. Furthermore, the treatment fully controlled infection after interruption of antiretroviral therapy in mice infected with different patient-derived polyclonal HIV-1 isolates.
This innovative approach offers a promising proof-of-principle for RNA-mediated bNAb immunotherapy in the fight against HIV-1 infection.
Written by urgent.news from bioRxiv's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
