关键词: Chikungunya SUMO Zika lumazine synthase nanoparticle nanovaccine

Mesh : Animals Mice Chikungunya virus / immunology Zika Virus / immunology Nanoparticles / chemistry Viral Vaccines / immunology chemistry Mice, Inbred BALB C Female Chikungunya Fever / immunology prevention & control Immunity, Humoral / drug effects Antibodies, Neutralizing / immunology Antigens, Viral / immunology chemistry Nanovaccines Multienzyme Complexes

来  源:   DOI:10.1002/adhm.202303619

Abstract:
The convergence strategies of antigenic subunits and synthetic nanoparticle scaffold platform improve the vaccine production efficiency and enhance vaccine-induced immunogenicity. Selecting the appropriate nanoparticle scaffold is crucial to controlling target antigens immunologically. Lumazine synthase (LS) is an attractive candidate for a vaccine display system due to its thermostability, modification tolerance, and morphological plasticity. Here, the first development of a multivalent thermostable scaffold, LS-SUMO (SUMO, small ubiquitin-likemodifier), and a divalent nanovaccine covalently conjugated with Chikungunya virus E2 and Zika virus EDIII antigens, is reported. Compared with antigen monomers, LS-SUMO nanoparticle vaccines elicit a higher humoral response and neutralizing antibodies against both antigen targets in mouse sera. Mice immunized with LS-SUMO conjugates produce CD4+ T cell-mediated Th2-biased responses and promote humoral immunity. Importantly, LS-SUMO conjugates possess equivalent humoral immunogenicity after heat treatment. Taken together, LS-SUMO is a powerful biotargeting nanoplatform with high-yield production, thermal stability and opens a new avenue for multivalent presentation of various antigens.
摘要:
抗原亚基和合成纳米支架平台的融合策略提高了疫苗生产效率,增强了疫苗诱导的免疫原性。选择合适的纳米颗粒支架对于靶抗原的免疫控制是关键的。由于其热稳定性,Lumazine合酶(LS)是疫苗展示系统的有吸引力的候选者,修改公差,和形态可塑性。这里,多价热稳定支架的首次开发,LS-SUMO,与CHIKVE2和ZIKVEDIII抗原共价结合的二价纳米疫苗,已报告。与抗原单体相比,LS-SUMO纳米颗粒疫苗在小鼠血清中引发针对两种抗原靶标的更高的体液应答和中和抗体。用LS-SUMO缀合物免疫的小鼠产生CD4+T细胞介导的Th2偏倚应答并促进体液免疫。重要的是,LS-SUMO缀合物在热处理后具有等效的体液免疫原性。一起来看,LS-SUMO是一个强大的生物靶向纳米平台,产量高,热稳定性,并为多种抗原的多价呈递开辟了新途径。本文受版权保护。保留所有权利。
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