Atomic-Scale Description of Interfaces between Antigen and Aluminum-Based Adjuvants used in Vaccines by DNP Enhanced NMR Spectroscopy

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 Al- gels and antigens is still missing. Here, we implement a new analytical approach based on Dynamic Nuclear Polarization (DNP) enhanced NMR spectroscopy under Magic Angle Spinning (MAS) to provide a molecular description of antigen-adjuvant interface. This approach is demonstrated on Hepatitis B surface antigen (HBsAg) particles in combination with three Al-gels obtained from different suppliers. Both non-covalent and covalent interactions between the phospholipids of the antigen particles and the surface of the Al-gels are identified by using MAS DNP NMR 27 Al and 31 P correlation experiments. While covalent interactions were detected for only one of the formulations, dipolar recoupling REAPDOR experiments reveal significant differences in the strength of weak interactions.