2023-07-25 カリフォルニア工科大学(Caltech)
◆ハイブリッド技術により、マウスの実験では2回の接種でオミクロン変異株に対する強力な抗体レベルが得られました。研究者たちはこの技術により、より効果的で持続性のあるワクチンの開発が期待できると述べています。
<関連情報>
- https://www.caltech.edu/about/news/new-vaccine-technology-produces-more-antibodies-against-sars-cov-2-in-mice
- https://www.cell.com/cell/fulltext/S0092-8674(23)00420-8
SARS-CoV-2スパイクへのESCRTのリクルートにより、mRNAワクチンを改善するウイルス様粒子が誘導される ESCRT recruitment to SARS-CoV-2 spike induces virus-like particles that improve mRNA vaccines
Magnus A.G. Hoffmann,Zhi Yang,Kathryn E. Huey-Tubman,Alexander A. Cohen,Priyanthi N.P. Gnanapragasam,Leesa M. Nakatomi,Kaya N. Storm,Woohyun J. Moon,Paulo J.C. Lin,Anthony P. West Jr.,Pamela J. Bjorkman
Cell Published:April 21, 2023
DOI:https://doi.org/10.1016/j.cell.2023.04.024
Highlights
•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
Summary
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.
