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J Nanobiotechnology . Double-layered N-S1 protein nanoparticle immunization elicits robust cellular immune and broad antibody responses against SAR

tetano

Editor, Senior Moderator
J Nanobiotechnology


. 2024 Jan 30;22(1):44.
doi: 10.1186/s12951-024-02293-y. Double-layered N-S1 protein nanoparticle immunization elicits robust cellular immune and broad antibody responses against SARS-CoV-2

Ruiqi Li[SUP] 1 2 3 4 [/SUP], Zejie Chang[SUP] 1 4 5 [/SUP], Hongliang Liu[SUP] 6 [/SUP], Yanan Wang[SUP] 4 5 [/SUP], Minghui Li[SUP] 4 5 [/SUP], Yilan Chen[SUP] 4 [/SUP], Lu Fan[SUP] 4 [/SUP], Siqiao Wang[SUP] 4 [/SUP], Xueke Sun[SUP] 4 5 [/SUP], Siyuan Liu[SUP] 4 5 [/SUP], Anchun Cheng[SUP] 1 [/SUP], Peiyang Ding[SUP] 7 [/SUP], Gaiping Zhang[SUP] 8 9 10 11 12 13 [/SUP]



Affiliations
Free article 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[SUP]+[/SUP] and CD8[SUP]+[/SUP] 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.

Keywords: COVID-19; Coronavirus; Nanoparticle; SARS-CoV-2; Subunit vaccine; Variants.

 
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