Wagner, A.A., et al. Accessing robust vaccine coformulation stability by single adjuvant detection on a microelectrode. Proc Natl Acad Sci U S A, 2025 Nov 4, 122(44):e2522044122.

Wagner, A.A., et al. Accessing robust vaccine coformulation stability by single adjuvant detection on a microelectrode. Proc Natl Acad Sci U S A, 2025 Nov 4, 122(44):e2522044122. PMID: 41150712

• The primary goal of this study is to develop and demonstrate a highly sensitive, single-particle analytical technique (stochastic electrochemistry) to assess the stability and interactions of complex vaccine formulations, specifically focusing on adjuvant-antigen coformulations like SHINGRIX™. Traditional methods such as dynamic light scattering (DLS) provide bulk measurements that can mask subtle nanoscale and microscale changes critical for ensuring vaccine efficacy and safety. By leveraging stochastic electrochemical blocking, the researchers aim to detect individual particle interactions, stability shifts, and heterogeneity within vaccine products over time, thereby offering a more detailed understanding of formulation stability. This approach addresses the need for precise, cell-level insights into vaccine components, which is vital for vaccine design, regulatory evaluation, and long-term quality control.
•  Key accomplishments include successfully detecting subtle size changes and heterogeneity within liposomal QS-21 adjuvanted vaccine formulations over time and under different storage conditions. Notably, the method revealed that while the AS01B adjuvant alone remains stable, significant size increases and distribution broadening occur when combined with the gE antigen at elevated temperatures, information that traditional bulk techniques might miss. Additionally, the technique identified interactions between vaccine components that were undetectable by DLS, offering a nuanced view of formulation stability and heterogeneity. 
• The limitations highlighted in the study include that stochastic electrochemical blocking is primarily a size-based technique and may not detect conformational changes or other particle characteristics unless these result in a size alteration. Additionally, the method’s sensitivity to subtle interactions depends on particle size and concentration ratios, which could limit its applicability in some complex vaccine formulations.
• Overall, these results showcase the potential of stochastic electrochemistry as a sensitive, label-free tool for real-time monitoring of vaccine integrity, stability, and compatibility at the single-particle level, advancing vaccine development and quality control. The study demonstrated that stochastic electrochemistry serves as a powerful, high-resolution complement to DLS for evaluating vaccine particle stability and interactions at the single-particle level.

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