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通过动态核极化(DNP)增强 NMR 光谱学研究疫苗中抗原与铝基佐剂之间界面的原子尺度描述。

Atomic-Scale Description of Interfaces between Antigen and Aluminum-Based Adjuvants Used in Vaccines by Dynamic Nuclear Polarization (DNP) Enhanced NMR Spectroscopy.

机构信息

Centre de résonance magnétique à très hauts champs (CRMN), FRE 2034 CNRS, Université Claude Bernard Lyon-1, ENS-Lyon, 5 rue de la Doua, 69100, Villeurbanne, France.

Institut des Sciences et Ingénierie Chimiques Batochime, École Polytechnique Fédérale de Lausanne (EPFL), 1530, Lausanne, Switzerland.

出版信息

Chemistry. 2020 Jul 22;26(41):8976-8982. doi: 10.1002/chem.202001141. Epub 2020 Jul 8.

DOI:10.1002/chem.202001141
PMID:32428253
Abstract

The addition of aluminum-based adjuvants in vaccines enhances the immune response to antigens. The strength of antigen adsorption on adjuvant gels is known to modulate vaccine efficacy. However, a detailed understanding of the mechanisms of interaction between aluminum gels and antigens is still missing. Herein, a new analytical approach based on dynamic nuclear polarization (DNP) enhanced NMR spectroscopy under magic angle spinning (MAS) is implemented to provide a molecular description of the antigen-adjuvant interface. This approach is demonstrated on hepatitis B surface antigen particles in combination with three aluminum gels obtained from different suppliers. Both noncovalent and covalent interactions between the phospholipids of the antigen particles and the surface of the aluminum gels are identified by using MAS DNP NMR Al and P correlation experiments. Although covalent interactions were detected for only one of the formulations, dipolar recoupling rotational echo adiabatic passage double resonance (REAPDOR) experiments reveal significant differences in the strength of weak interactions.

摘要

疫苗中添加铝基佐剂可增强对抗原的免疫应答。已知佐剂凝胶对抗原的吸附强度可调节疫苗的效力。然而,对于铝凝胶和抗原之间相互作用的机制仍缺乏详细的了解。在此,我们实施了一种基于动态核极化(DNP)增强魔角旋转(MAS)NMR 光谱的新分析方法,以提供抗原-佐剂界面的分子描述。该方法结合三种不同供应商的铝凝胶,应用于乙肝表面抗原颗粒。通过 MAS DNP NMR ^1 Al 和 ^31 P 相关实验,确定了抗原颗粒的磷脂与铝凝胶表面之间的非共价和共价相互作用。尽管仅在一种配方中检测到共价相互作用,但偶极子重聚旋转回波绝热通道双共振(REAPDOR)实验揭示了弱相互作用强度的显著差异。

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