Intranasal inoculation of female BALB/c mice with replication-deficient human adenovirus type 5 expressing SARS-CoV‐2 nucleocapsid protein aggravates lung pathology upon re-encountering the antigen

Preclinical studies indicate that SARS-CoV-2 nucleocapsid (N)-based vaccines, along with other viral protein(s), confer protection in various animal models against infection by SARS-CoV-2 ancestral virus and variants of concern. However, the optimal vaccination procedure and the role of N-specific h...

Full description

Bibliographic Details
Main Authors: Junxia Cao, Hongjing Gu, Xueting Zhang, Hongfang Yun, Jiarong Li, Chuan-Yimu Si, Jiyan Zhang, Hui Wang
Format: Article
Language:English
Published: Elsevier 2023-10-01
Series:Virus Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0168170223001636
Description
Summary:Preclinical studies indicate that SARS-CoV-2 nucleocapsid (N)-based vaccines, along with other viral protein(s), confer protection in various animal models against infection by SARS-CoV-2 ancestral virus and variants of concern. However, the optimal vaccination procedure and the role of N-specific host adaptive immune responses remain elusive. Here, we report that intranasal inoculation with replication-deficient human adenovirus type 5 expressing SARS-CoV‐2 N protein (Ad5-N) conferred no protection in the lung of female BALB/c mice upon re-encountering the antigen, either by 10-fold Ad5-N re-exposure or sublethal infection of mouse-adapted SARS-CoV-2. By contrast, this procedure led to aggravated lung pathology with more necroptotic CD3+ T cells and Ly6G+ granulocytes, which was associated with the accumulation of IFN‐γ‐expressing antigen-experienced CD4+ and CD8+ T cells. These findings pre-caution the clinical application of this vaccination procedure. Furthermore, our data suggest that excessive host adaptive immune responses against N protein contributes to COVID-19 pathogenesis.
ISSN:1872-7492