Cheng Cheng, Boyington Jeffrey C, Sarfo Edward K, Liu Cuiping, Parchment Danealle K, Biju Andrea, Corrigan Angela R, Wang Lingshu, Shi Wei, Zhang Yi, Tsybovsky Yaroslav, Stephens Tyler, Olia Adam S, Carson Audrey S, Moin Syed M, Yang Eun Sung, Zhang Baoshan, Kong Wing-Pui, Kwong Peter D, Mascola John R, Pierson Theodore C
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Vaccines (Basel). 2025 Jul 23;13(8):780. doi: 10.3390/vaccines13080780.
Vaccines that stimulate systemic and mucosal immunity to a level required to prevent SARS-CoV-2 infection and transmission are an unmet need. Highly protective hepatitis B and human papillomavirus nanoparticle vaccines highlight the potential of multivalent nanoparticle vaccine platforms to provide enhanced immunity. Here, we report the construction and characterization of self-assembling 60-subunit icosahedral nanoparticle SARS-CoV-2 vaccines using the bacterial enzyme lumazine synthase (LuS). Nanoparticles displaying prefusion-stabilized SARS-CoV-2 spike ectodomains fused to the surface-exposed amino terminus of LuS were designed using structure-guided approaches. Negative stain-electron microscopy studies of purified nanoparticles were consistent with self assembly into 60-mer nanoparticles displaying 20 spike trimers. After two intramuscular doses, these purified spike-LuS nanoparticles elicited significantly higher SARS-CoV-2 neutralizing activity than spike trimers in vaccinated mice. Furthermore, intramuscular DNA priming and intranasal boosting with a SARS-CoV-2 LuS nanoparticle vaccine stimulated mucosal IgA responses. These data identify LuS nanoparticles as highly immunogenic SARS-CoV-2 vaccine candidates and support the further development of this platform against SARS-CoV-2 and its emerging variants.
能够将全身和黏膜免疫刺激到预防SARS-CoV-2感染和传播所需水平的疫苗是尚未满足的需求。高度保护性的乙肝和人乳头瘤病毒纳米颗粒疫苗凸显了多价纳米颗粒疫苗平台提供增强免疫力的潜力。在此，我们报告了使用细菌酶核黄素合酶（LuS）构建和表征自组装60亚基二十面体纳米颗粒SARS-CoV-2疫苗的情况。利用结构导向方法设计了展示与LuS表面暴露的氨基末端融合的预融合稳定SARS-CoV-2刺突胞外域的纳米颗粒。对纯化纳米颗粒的负染色电子显微镜研究结果与自组装成展示20个刺突三聚体的60聚体纳米颗粒一致。在接种小鼠中，经过两次肌肉注射剂量后，这些纯化的刺突-LuS纳米颗粒引发的SARS-CoV-2中和活性显著高于刺突三聚体。此外，用SARS-CoV-2 LuS纳米颗粒疫苗进行肌肉内DNA初免和鼻内加强免疫可刺激黏膜IgA反应。这些数据确定LuS纳米颗粒是具有高度免疫原性的SARS-CoV-2疫苗候选物，并支持该平台针对SARS-CoV-2及其新出现变体的进一步开发。
