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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...

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Detalles Bibliográficos
Autores principales: Cao, Junxia, Gu, Hongjing, Zhang, Xueting, Yun, Hongfang, Li, Jiarong, Si, Chuan-Yimu, Zhang, Jiyan, Wang, Hui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10470087/
https://www.ncbi.nlm.nih.gov/pubmed/37595663
http://dx.doi.org/10.1016/j.virusres.2023.199201
Descripción
Sumario: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.