1. Double-layered N-S1 protein nanoparticle immunization elicits robust cellular immune and broad antibody responses against SARS-CoV-2.
- Author
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Li, Ruiqi, Chang, Zejie, Liu, Hongliang, Wang, Yanan, Li, Minghui, Chen, Yilan, Fan, Lu, Wang, Siqiao, Sun, Xueke, Liu, Siyuan, Cheng, Anchun, Ding, Peiyang, and Zhang, Gaiping
- Subjects
NANOPARTICLES ,ANTIBODY formation ,SARS-CoV-2 ,SOLVABLE groups ,HUMORAL immunity ,T cells ,AVIAN influenza - Abstract
Background: The COVID-19 pandemic is a persistent global threat to public health. As for the emerging variants of SARS-CoV-2, it is necessary to develop vaccines that can induce broader immune responses, particularly vaccines with weak cellular immunity. Methods: In this study, we generated a double-layered N-S1 protein nanoparticle (N-S1 PNp) that was formed by desolvating N protein into a protein nanoparticle as the core and crosslinking S1 protein onto the core surface against SARS-CoV-2. Results: Vaccination with N-S1 PNp elicited robust humoral and vigorous cellular immune responses specific to SARS-CoV-2 in mice. Compared to soluble protein groups, the N-S1 PNp induced a higher level of humoral response, as evidenced by the ability of S1-specific antibodies to block hACE2 receptor binding and neutralize pseudovirus. Critically, N-S1 PNp induced Th1-biased, long-lasting, and cross-neutralizing antibodies, which neutralized the variants of SARS-CoV-2 with minimal loss of activity. N-S1 PNp induced strong responses of CD4
+ and CD8+ T cells, mDCs, Tfh cells, and GCs B cells in spleens. Conclusions: These results demonstrate that N-S1 PNp vaccination is a practical approach for promoting protection, which has the potential to counteract the waning immune responses against SARS-CoV-2 variants and confer broad efficacy against future new variants. This study provides a new idea for the design of next-generation SARS-CoV-2 vaccines based on the B and T cells response coordination. [ABSTRACT FROM AUTHOR]- Published
- 2024
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