DNP-enhanced solid-state NMR: a unique technique to investigate vaccine formulations

Challenge: In vaccine formulations, aluminum-based adjuvants are crucial for boosting the immune response. However, the exact nature of how these adjuvants interact with antigens, which impacts vaccine efficacy, has been poorly understood. Understanding these interactions at the atomic level is essential for improving vaccine design and production.

NMR solution: A DNP-enhanced solid-state NMR study done with academic researchers and SANOFI Pasteur provided the first molecular-level insight into the interaction between hepatitis B surface antigens and aluminum gels. By applying 27Al and 31P NMR correlation experiments, the team uncovered both covalent and noncovalent interactions between the antigen’s phospholipids and the surface of the adjuvant particles. Notably, they identified differences in electrostatic interactions across aluminum gels from various providers, using dipolar recoupling experiments to assess the strength of these weak interactions.

Impact: This novel approach not only revealed critical differences in the interaction between various aluminum gels and the antigens. These interactions influence the antigen release and, ultimately, the immune response. Thus, a deeper understanding of the antigen-adjuvant interface opens new possibilities for optimizing vaccine formulations, making them more effective and tailored to specific needs. DNP-enhanced NMR was essential in this research, offering unprecedented sensitivity in studying these complex assemblies.

Key Points for industry:
  • Improved Vaccine Design: By revealing how aluminum gels interact differently with antigens, this study provides unique insight that could be used to enhance vaccine efficacy.
  • Cutting-Edge NMR Technology: The use of DNP-enhanced NMR opens new avenues for rapid and detailed analysis of complex interfaces, streamlining vaccine development.
  • Tailored Formulations: Understanding antigen-adjuvant interactions can lead to better-designed vaccines, ensuring stronger and more controlled immune responses.

Reference: Viger-Gravel, J.; Paruzzo, F. M.; Cazaux, C.; Jabbour, R.; Leleu, A.; Canini, F.; Florian, P.; Ronzon, F.; Gajan, D.; Lesage, A. Atomic-Scale Description of Interfaces between Antigen and Aluminum-Based Adjuvants Used in Vaccines by Dynamic Nuclear Polarization (DNP) Enhanced NMR Spectroscopy. Chem.-Eur. J. 2020, 26, 8976–8982.

https://doi.org/10.1002/chem.202001141.

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Figure: 27Al and 31P DNP NMR spectra of HBsAg antigen on aluminum adjuvant gels. Adapted from Viger-Gravel et al, Chem.-Eur. J. 2020, 26, 8976–8982.