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Th2 and Th17-Associated Immunopathology Following SARS-CoV-2 Breakthrough Infection in Spike-Vaccinated ACE2-humanized Mice.

Tianyi ZhangNicholas MagazineMichael C McGeeMariano CarossinoGianluca VeggianiKonstantin G KousoulasAvery AugustWeishan Huang
Published in: bioRxiv : the preprint server for biology (2023)
This research investigates the safety and efficacy of a Spike protein subunit vaccine adjuvanted with Alum and CpG in an ACE2-humanized mouse model, simulating SARS-CoV-2 breakthrough infections. The study reveals that despite robust protection against severe COVID-19, vaccinated mice exhibit substantial pulmonary immunopathology, including eosinophilia and enhanced Th2 effector immunity, following breakthrough infections. Surprisingly, the study also uncovers a significant systemic Th17 inflammatory response in vaccinated mice. This research sheds light on the potential risks associated with COVID-19 vaccine breakthrough infections and the need for a comprehensive understanding of vaccine-induced immune responses, emphasizing the importance of ongoing research, surveillance, and careful vaccine development for both protection and safety in the fight against the COVID-19 pandemic.
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