Details

Autor(en) / Beteiligte

• Hoffmann, Magnus A.G.
• Yang, Zhi
• Huey-Tubman, Kathryn E.
• Cohen, Alexander A.
• Gnanapragasam, Priyanthi N.P.
• Nakatomi, Leesa M.
• Storm, Kaya N.
• Moon, Woohyun J.
• Lin, Paulo J.C.
• West, Anthony P.
• Bjorkman, Pamela J.

Titel

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

Ist Teil von

• Cell, 2023-05, Vol.186 (11), p.2380-2391.e9

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2023

Quelle

Elektronische Zeitschriftenbibliothek - Freely accessible e-journals

Beschreibungen/Notizen

• 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. [Display omitted] •EABR technology engineers membrane proteins to induce assembly of enveloped VLPs•SARS-CoV-2 spike-EABR eVLPs were genetically encoded and delivered as mRNA vaccine•Spike-EABR mRNA elicits higher antibody titers than conventional spike mRNA in mice•Spike-EABR mRNA elicits potent antibody responses against Omicron variants The SARS-CoV-2 spike protein was engineered to recruit ESCRT proteins to its cytoplasmic tail by adding an EABR motif, which induced the assembly of enveloped virus-like particles. A COVID-19 mRNA vaccine encoding spike-EABR elicited superior antibody responses compared with a conventional mRNA vaccine in mice.