ESCRT recruitment to SARS-CoV-2 spike induces virus-like particles that improve mRNA vaccines

Cell. 2023 May 25;186(11):2380-2391.e9. doi: 10.1016/j.cell.2023.04.024. Epub 2023 Apr 21.


Prime-boost regimens for COVID-19 vaccines elicit poor antibody responses against Omicron-based variants and employ frequent boosters to maintain antibody levels. We present a natural infection-mimicking technology that combines features of mRNA- and protein nanoparticle-based vaccines through encoding self-assembling enveloped virus-like particles (eVLPs). eVLP assembly is achieved by inserting an ESCRT- and ALIX-binding region (EABR) into the SARS-CoV-2 spike cytoplasmic tail, which recruits ESCRT proteins to induce eVLP budding from cells. Purified spike-EABR eVLPs presented densely arrayed spikes and elicited potent antibody responses in mice. Two immunizations with mRNA-LNP encoding spike-EABR elicited potent CD8+ T cell responses and superior neutralizing antibody responses against original and variant SARS-CoV-2 compared with conventional spike-encoding mRNA-LNP and purified spike-EABR eVLPs, improving neutralizing titers >10-fold against Omicron-based variants for 3 months post-boost. Thus, EABR technology enhances potency and breadth of vaccine-induced responses through antigen presentation on cell surfaces and eVLPs, enabling longer-lasting protection against SARS-CoV-2 and other viruses.

Keywords: ESCRT; SARS-CoV-2; mRNA vaccines; nanoparticles.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines*
  • COVID-19* / prevention & control
  • Endosomal Sorting Complexes Required for Transport
  • Humans
  • Mice
  • RNA, Messenger
  • SARS-CoV-2
  • mRNA Vaccines*


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines
  • Endosomal Sorting Complexes Required for Transport
  • mRNA Vaccines
  • RNA, Messenger