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Broad anti-sarbecovirus responses elicited by a single administration of mosaic-8 RBD-nanoparticle vaccine prepared using atomic layer deposition

作者:Alexander A. Cohen, Jennifer R. Keeffe, Annie V. Rorick, Semi Rho, Ange-Célia Priso Fils, Lusineh Manasyan, Han Gao, Priyanthi N.P. Gnanapragasam, Hans H. Funke, Theodore W. Randolph, Robert L. Garcea, Pamela J. Björkman · 发表于:iScience · 年份:2025 · DOI:10.1016/j.isci.2025.113649 · 被引用次数:6 · 研究领域:Advanced Biosensing Techniques and Applications、Respiratory viral infections research、SARS-CoV-2 and COVID-19 Research

Atomic layer deposition (ALD), a new vaccine technology, permits multiple dosing with a single administration by pulsatile release of one or more immunogens. We evaluated ALD delivery of mosaic-8b [60-mer nanoparticles presenting 8 different SARS-like betacoronavirus (sarbecovirus) receptor-binding domains (RBDs)] that elicit broadly cross-reactive antibodies and protect against mismatched sarbecoviruses not represented by RBDs on mosaic-8b. Compared with conventional prime-boost immunizations, ALD-delivered mosaic-8b RBD-nanoparticles elicited antibodies in both naive and pre-vaccinated mice with improved mismatched binding and neutralization. Results of the RBD epitope mapping of serum antibodies from ALD-delivered mosaic-8b were consistent with broader coverage of RBD epitopes compared to conventional immunizations, and systems serology revealed distinct IgG subclass and FcγR-binding IgG distributions. These results suggest that ALD is a promising technology for use with mosaic-8b RBD-nanoparticle vaccines to protect against future sarbecovirus spillovers and support applications for ALD vaccine delivery to elicit cross-reactive antibodies against rapidly mutating or diverse pathogens.