Durable suppression of viremia by lipid nanoparticle-formulated RNA encoding for a highly potent HIV-1…

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 ug RNA-LNP intravenous injection resulted in an average peak 1-18-LS RibobNAb serum concentration of 1,061 ug/mL in human neonatal Fc receptor-transgenic mice. Notably, weekly 30 ug RNA-LNP doses maintained higher trough bNAb levels than 500 ug protein injections. Highlighting potent antiviral activity, RNA-LNP-mediated 1-18-LS RibobNAb monotherapy of viremic HIV-1YU2-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.

Enhanced Neutralizing Antibody Responses to Rhinovirus C and Age-Dependent Patterns of Infection
T. Choi, M. Devries, L. B. Bacharier +39
American Journal of Respiratory and Critical Care Medicine9 Oct 2026Peer-reviewedLicence not stated44 citedMicrobiologyHAL
Prophylactic treatment with broadly neutralizing antibody VRC01 selects for escape mutants after infection in Antibody-Mediated Prevention trials
Carolyn Williamson, Lyle Curry, Nonhlanhla N. Mkhize +46
Nature Microbiology28 Sep 2026Peer-reviewedCC BY 4.0Full textMicrobiologyPMC
Epistasis and pleiotropy constrain the evolution of cross-reactive breadth in a broadly neutralizing influenza antibody
Katrine E. Dailey, Yiquan Wang, Qi Wen Teo +7
PLOS Biology28 Sep 2026Peer-reviewedCC BY 4.0Full textGenetics & genomics ImmunologyPLOS
Near real-time data on the human neutralizing antibody landscape to influenza virus in summer of 2026 shows antigenic advance of H3N2 subclade K region D mutants and H1N1 D.3.1.1 Sa mutants
C. Kikawa, A. Butler, J. Huddleston +16
bioRxiv15 Sep 2026PreprintCC BYFull text1 citedMicrobiologybioRxiv
Eastern equine encephalitis virus-vaccinated mice are protected against Madariaga virus despite negligible neutralizing antibody titers
S. Cerezo, C.-H. Sung, W. Tang +3
bioRxiv14 Sep 2026PreprintCC BYFull textSystems & synthetic biologybioRxiv

Cite

BibTeX RIS

BibTeX

@misc{sayettat2026durable,
  title = {{Durable suppression of viremia by lipid nanoparticle-formulated RNA encoding for a highly potent HIV-1 neutralizing antibody}},
  author = {S. Sayettat and F. Tolksdorf and R. Johannson and J. Nelke and A. Malz and L. Fischer and I. Gerhard and N. Ullrich and U. Ellinghaus and C. R. Stadler and J. P. Bogen and C. Morin and J. Knüfer and R. Stumpf and P. Schommers and U. Sahin and M. S. Seaman and S. Kratochvil and F. Klein and V. Le Douce and H. Gruell},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.17.752120},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.17.752120v1},
  note = {CC BY-NC-ND},
}

RIS

TY  - UNPB
TI  - Durable suppression of viremia by lipid nanoparticle-formulated RNA encoding for a highly potent HIV-1 neutralizing antibody
AU  - S. Sayettat
AU  - F. Tolksdorf
AU  - R. Johannson
AU  - J. Nelke
AU  - A. Malz
AU  - L. Fischer
AU  - I. Gerhard
AU  - N. Ullrich
AU  - U. Ellinghaus
AU  - C. R. Stadler
AU  - J. P. Bogen
AU  - C. Morin
AU  - J. Knüfer
AU  - R. Stumpf
AU  - P. Schommers
AU  - U. Sahin
AU  - M. S. Seaman
AU  - S. Kratochvil
AU  - F. Klein
AU  - V. Le Douce
AU  - H. Gruell
PY  - 2026
DA  - 2026/09/17
PB  - bioRxiv
DO  - 10.64898/2026.09.17.752120
UR  - https://www.biorxiv.org/content/10.64898/2026.09.17.752120v1
AB  - 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 peak 1-18-LS RibobNAb serum concentration of 1,061 ug/mL in human neonatal Fc receptor-transgenic mice. Notably, weekly 30 ug RNA-LNP doses maintained higher trough bNAb levels than 500 ug protein injections. Highlighting potent antiviral activity, RNA-LNP-mediated 1-18-LS RibobNAb monotherapy of viremic HIV-1YU2-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.
ER  -

Abstract

Related

Cite