Lipid nanoparticle-encapsulated mRNA antibody provides long-term protection against SARS-CoV-2 in mice and hamsters

Cell Res. 2022 Apr;32(4):375-382. doi: 10.1038/s41422-022-00630-0. Epub 2022 Feb 24.

Abstract

Monoclonal antibodies represent important weapons in our arsenal to against the COVID-19 pandemic. However, this potential is severely limited by the time-consuming process of developing effective antibodies and the relative high cost of manufacturing. Herein, we present a rapid and cost-effective lipid nanoparticle (LNP) encapsulated-mRNA platform for in vivo delivery of SARS-CoV-2 neutralization antibodies. Two mRNAs encoding the light and heavy chains of a potent SARS-CoV-2 neutralizing antibody HB27, which is currently being evaluated in clinical trials, were encapsulated into clinical grade LNP formulations (named as mRNA-HB27-LNP). In vivo characterization demonstrated that intravenous administration of mRNA-HB27-LNP in mice resulted in a longer circulating half-life compared with the original HB27 antibody in protein format. More importantly, a single prophylactic administration of mRNA-HB27-LNP provided protection against SARS-CoV-2 challenge in mice at 1, 7 and even 63 days post administration. In a close contact transmission model, prophylactic administration of mRNA-HB27-LNP prevented SARS-CoV-2 infection between hamsters in a dose-dependent manner. Overall, our results demonstrate a superior long-term protection against SARS-CoV-2 conferred by a single administration of this unique mRNA antibody, highlighting the potential of this universal platform for antibody-based disease prevention and therapy against COVID-19 as well as a variety of other infectious diseases.

Trial registration: ClinicalTrials.gov NCT03829384.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / therapeutic use
  • Antibodies, Viral / therapeutic use
  • COVID-19* / prevention & control
  • Cricetinae
  • Humans
  • Liposomes
  • Mice
  • Nanoparticles
  • Pandemics / prevention & control
  • RNA, Messenger / genetics
  • SARS-CoV-2*
  • Spike Glycoprotein, Coronavirus

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Lipid Nanoparticles
  • Liposomes
  • RNA, Messenger
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2

Associated data

  • ClinicalTrials.gov/NCT03829384