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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