Double-layered N-S1 protein nanoparticle immunization elicits robust cellular immune and broad antibody responses against SARS-CoV-2
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. Graphical Abstract Steps involved in the preparation of double-layered N-S1 protein nanoparticle vaccines and experimental design performed in combating virus infection. After intramuscular immunization of mice, the double-layered N-S1 protein nanovaccine could effectively promote the maturation of antigen-presenting and mature dendritic cells, robust broad-spectrum neutralizing antibody production, cytokines secretion, robust mDC, Tfh cell, and GCs B cell responses induction, T-cell memory formation and durable antibody responses, and unique global transcriptome characteristics, thus achieving a robust cellular immunity and broad antibody responses against SARS-CoV-2 based on the B and T cells response coordination.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:22 |
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| Enthalten in: |
Journal of nanobiotechnology - 22(2024), 1 vom: 30. Jan. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Ruiqi [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| Themen: |
COVID-19 |
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| Anmerkungen: |
© The Author(s) 2024 |
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| doi: |
10.1186/s12951-024-02293-y |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a 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. Graphical Abstract Steps involved in the preparation of double-layered N-S1 protein nanoparticle vaccines and experimental design performed in combating virus infection. After intramuscular immunization of mice, the double-layered N-S1 protein nanovaccine could effectively promote the maturation of antigen-presenting and mature dendritic cells, robust broad-spectrum neutralizing antibody production, cytokines secretion, robust mDC, Tfh cell, and GCs B cell responses induction, T-cell memory formation and durable antibody responses, and unique global transcriptome characteristics, thus achieving a robust cellular immunity and broad antibody responses against SARS-CoV-2 based on the B and T cells response coordination | ||
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| 700 | 1 | |a Chang, Zejie |4 aut | |
| 700 | 1 | |a Liu, Hongliang |4 aut | |
| 700 | 1 | |a Wang, Yanan |4 aut | |
| 700 | 1 | |a Li, Minghui |4 aut | |
| 700 | 1 | |a Chen, Yilan |4 aut | |
| 700 | 1 | |a Fan, Lu |4 aut | |
| 700 | 1 | |a Wang, Siqiao |4 aut | |
| 700 | 1 | |a Sun, Xueke |4 aut | |
| 700 | 1 | |a Liu, Siyuan |4 aut | |
| 700 | 1 | |a Cheng, Anchun |4 aut | |
| 700 | 1 | |a Ding, Peiyang |4 aut | |
| 700 | 1 | |a Zhang, Gaiping |4 aut | |
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