Lipid Nanoparticle RBD-hFc mRNA Vaccine Protects hACE2 Transgenic Mice against a Lethal SARS-CoV-2 Infection

Uri Elia, Shahar Rotem, Erez Bar-Haim, Srinivas Ramishetti, Gonna Somu Naidu, David Gur, Moshe Aftalion, Ma'ayan Israeli, Adi Bercovich-Kinori, Ron Alcalay, Efi Makdasi, Theodor Chitlaru, Ronit Rosenfeld, Tomer Israely, Sharon Melamed, Inbal Abutbul Ionita, Dganit Danino, Dan Peer, Ofer Cohen

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The COVID-19 pandemic led to development of mRNA vaccines, which became a leading anti-SARS-CoV-2 immunization platform. Preclinical studies are limited to infection-prone animals such as hamsters and monkeys in which protective efficacy of vaccines cannot be fully appreciated. We recently reported a SARS-CoV-2 human Fc-conjugated receptor-binding domain (RBD-hFc) mRNA vaccine delivered via lipid nanoparticles (LNPs). BALB/c mice demonstrated specific immunologic responses following RBD-hFc mRNA vaccination. Now, we evaluated the protective effect of this RBD-hFc mRNA vaccine by employing the K18 human angiotensin-converting enzyme 2 (K18-hACE2) mouse model. Administration of an RBD-hFc mRNA vaccine to K18-hACE2 mice resulted in robust humoral responses comprising binding and neutralizing antibodies. In correlation with this response, 70% of vaccinated mice withstood a lethal SARS-CoV-2 dose, while all control animals succumbed to infection. To the best of our knowledge, this is the first nonreplicating mRNA vaccine study reporting protection of K18-hACE2 against a lethal SARS-CoV-2 infection.

Original languageEnglish (US)
Pages (from-to)4774-4779
Number of pages6
JournalNano Letters
Volume21
Issue number11
DOIs
StatePublished - Jun 9 2021

Keywords

  • COVID-19
  • SARS-CoV-2
  • ionizable lipids
  • lipid nanoparticles
  • mRNA vaccine

ASJC Scopus subject areas

  • Bioengineering
  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics
  • Mechanical Engineering

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