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Double-layered N-S1 protein nanoparticle immunization elicits robust cellular immune and broad antibody responses against SARS-CoV-2

文献类型： 外文期刊

作者： Li, Ruiqi 1 ; Chang, Zejie 1 ; Liu, Hongliang 6 ; Wang, Yanan 4 ; Li, Minghui 4 ; Chen, Yilan 4 ; Fan, Lu 4 ; Wang, Siqiao 4 ; Sun, Xueke 4 ; Liu, Siyuan 4 ; Cheng, Anchun 1 ; Ding, Peiyang 6 ; Zhang, Gaiping 1 ;

作者机构： 1.Sichuan Agr Univ, Coll Vet Med, Chengdu 611130, Peoples R China

2.Peking Univ, Sch Adv Agr Sci, Beijing 100080, Peoples R China

3.Longhu Lab, Zhengzhou 450046, Peoples R China

4.Henan Acad Agr Sci, Henan Prov Key Lab Anim Immunol, Zhengzhou 450002, Peoples R China

5.Henan Agr Univ, Coll Anim Med, Zhengzhou 450046, Peoples R China

6.Zhengzhou Univ, Sch Life Sci, Zhengzhou 450001, Peoples R China

关键词： COVID-19; Coronavirus; SARS-CoV-2; Nanoparticle; Subunit vaccine; Variants

期刊名称：JOURNAL OF NANOBIOTECHNOLOGY （ 影响因子：10.2； 五年影响因子：11.5 ）

ISSN：

年卷期： 2024 年 22 卷 1 期

页码：

收录情况： SCI

摘要： BackgroundThe 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.MethodsIn 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.ResultsVaccination 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.ConclusionsThese 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 AbstractSteps 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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