Accessing robust vaccine coformulation stability by single adjuvant detection on a microelectrode

A significant question in next generation vaccine development is: How long are coformulated products stable on the shelf? The recent review by the US Food and Drug Administration of a single, prefilled syringe of the SHINGRIX™ vaccine has highlighted the importance of this question. While dynamic light scattering is well suited for measuring average particle sizes across populations, fundamental principles behind scattering limit the resolution to distinguish subtle differences at the tens of nanometer scale between similar samples. To address this, we introduce an alternative approach: stochastic electrochemistry, which allows for the investigation of specific properties of individual particles, one at a time. By introducing an electrochemically active species, hexacyanoferrate(II/III) into the vaccine solution, we observe discrete current drops when particles irreversibly collide with a microelectrode. Such events can be correlated directly with particle size. As a proof of concept, we use this technique to analyze the interactions of streptavidin-functionalized poly(lactic-co-glycolic acid) beads with biotinylated bovine serum albumin at vaccine-level concentrations and apply what we learned to the components of the SHINGRIX™ vaccine. We then present a time-trial comparison of data from current commercial SHINGRIX™ vaccines using dynamic light scattering and stochastic electrochemistry, analyzing the AS01_B adjuvant alone and the AS01_B adjuvant combined with the glycoprotein E (gE protein). While our method elucidates important properties at the single adjuvant level, our results paint a quantitative kinetic picture of coformulation stability that is currently not achievable by dynamic light scattering.