This study encoded the potent broadly neutralizing antibody 1-18-LS as messenger RNA and formulated it in lipid nanoparticles (LNPs) to generate an RNA-encoded bNAb product called 1-18-LS RibobNAb. The approach was tested as an alternative to conventional recombinant antibody production, with the objective of achieving robust in vivo expression of a highly potent bNAb and evaluating antiviral efficacy against HIV-1 in mouse models that support human antibody pharmacology and HIV-1 replication.
The report presents data from intravenous administrations of the RNA-LNP formulation and compares results to direct protein (recombinant antibody) injections in relevant mouse models. Details on formulation specifics, manufacturing processes, and full methods are reported in the source preprint; additional methodological granularity beyond what is summarized here was not reported in the provided abstract.
A single intravenous injection of 30 µg of the RNA-LNP encoding 1-18-LS produced high in vivo antibody expression in human neonatal Fc receptor-transgenic mice, with an average peak serum concentration reported as 1,061 µg/mL. This finding indicates efficient translation and secretion of the encoded antibody following RNA-LNP delivery.
The authors compared repeat dosing regimens and found that weekly administration of 30 µg RNA-LNP doses maintained higher trough serum levels of the bNAb than did much larger 500 µg protein (recombinant antibody) injections. This comparison highlights a potential pharmacokinetic advantage of RNA-mediated in vivo expression over bolus protein administration, at least in the reported animal models and dose ranges.
To assess antiviral activity, the study evaluated RNA-LNP-mediated 1-18-LS RibobNAb as monotherapy in viremic humanized mice infected with the HIV-1 YU2 strain. The treatment resulted in durable suppression of HIV-1 viremia in these animals. Importantly, within the reported experiments, suppression occurred without the emergence of detectable viral escape variants, indicating potent antiviral pressure and maintained neutralizing activity of the expressed antibody over the study period described in the source.
The use of humanized mice enabled assessment of both in vivo antibody pharmacology and antiviral effects in an immunologically relevant small-animal platform. Specific timelines for viral load decline, duration of follow-up, and detailed viral sequencing data supporting the absence of escape were provided in the full preprint; the abstract summarized the key outcomes as durable suppression without emerging escape.
Beyond the YU2 monotherapy experiments, the authors tested 1-18-LS RNA-LNP in humanized mice infected with different patient-derived polyclonal HIV-1 isolates. In these models, treatment with the RNA-LNP encoding 1-18-LS fully controlled infection after interruption of antiretroviral therapy (ART), demonstrating antiviral efficacy across multiple viral backgrounds in the reported experiments.
These findings suggest that RNA-mediated delivery of a potent bNAb can sustain antiviral control even after stopping ART in the tested preclinical models, supporting the concept of RNA-encoded immunotherapy as a functional approach to control viremia.
The experiments provide a proof-of-principle that systemic delivery of RNA encoding a highly potent HIV-1 neutralizing antibody via LNPs can achieve high serum antibody concentrations, maintain superior trough levels compared with large protein doses in these models, and deliver durable antiviral effects without detected viral escape in the contexts studied.
This approach could address manufacturing and supply limitations associated with recombinant bNAb therapies by enabling in vivo production of therapeutic antibodies from an RNA template. However, the report is a preclinical study in mouse models; translational considerations such as dosing, safety, immunogenicity, durability, and efficacy in humans will require further investigation. The source abstract does not report long-term safety data, clinical trial outcomes, or larger-animal studies; those details were not reported in the provided summary.
The authors disclosed multiple competing interests: several contributors are employees of BioNTech and may hold stock options; some are inventors on patents related to RNA-encoded anti-HIV antibodies and specific neutralizing antibody candidates. Additional reported relationships include patent licensing and consulting. Funding sources declared in the preprint included the Deutsche Forschungsgemeinschaft (Emmy Noether Program), Else Kröner-Fresenius-Stiftung, the German Center for Infection Research, and BioNTech.
Readers should note that the work is reported as a bioRxiv preprint and that the summary here is limited to the findings and disclosures presented in the source. Further peer-reviewed publications and additional data will be needed to fully evaluate translational potential and safety.