A genetically engineered, stem-cell-derived cellular vaccine

一种基因工程干细胞衍生细胞疫苗

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作者:Amanda Cooper,Adam Sidaway,Abishek Chandrashekar,Elizabeth Latta,Krishnendu Chakraborty,Jingyou Yu,Katherine McMahan,Victoria Giffin,Cordelia Manickam,Kyle Kroll,Matthew Mosher,R Keith Reeves,Rihab Gam,Elisa Arthofer,Modassir Choudhry,Tom Henley,Dan H Barouch

Abstract

Despite rapid clinical translation of COVID-19 vaccines in response to the global pandemic, an opportunity remains for vaccine technology innovation to address current limitations and meet challenges of inevitable future pandemics. We describe a universal vaccine cell (UVC) genetically engineered to mimic natural physiological immunity induced upon viral infection of host cells. Cells engineered to express the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike as a representative viral antigen induce robust neutralizing antibodies in immunized non-human primates. Similar titers generated in this established non-human primate (NHP) model have translated into protective human neutralizing antibody levels in SARS-CoV-2-vaccinated individuals. Animals vaccinated with ancestral spike antigens and subsequently challenged with SARS-CoV-2 Delta variant in a heterologous challenge have an approximately 3 log decrease in viral subgenomic RNA in the lungs. This cellular vaccine is designed as a scalable cell line with a modular poly-antigenic payload, allowing for rapid, large-scale clinical manufacturing and use in an evolving viral variant environment.

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