Applying Microfluidic Modulation Spectroscopy in Vaccine Formulation to Identify Intermolecular Beta-sheet Aggregation of Antigens

American Pharmaceutical Review

Patrick L. Ahl, Garrett Baird, Christopher Farrell, William J. Smith, Jeffrey Blue, and Libo Wang

Vaccines are a cornerstone of modern medicine and have been successfully deployed to substantially reduce the threat posed by infectious diseases such as diphtheria, hepatitis, and polio. While COVID 19 is currently the focus of intense vaccine development activity, diseases such as malaria and HIV remain important ongoing targets; vaccines to reduce the impact of cancer are also a long term goal. Successful vaccination relies on introducing an antigen into the body that ‘trains’ it to produce antibodies in the event of a subsequent encounter with a specific virus or bacteria. Commercial vaccine formulations include adjuvants, antibiotics, preservatives, and stabilizers to ensure safe delivery of the intact antigen to the patient, and to maximize effectiveness. In this article we consider the potential impact of antigen unfolding and aggregation in vaccine formulations and the techniques available for detection and application in formulation studies. A primary focus is the use of Microfluidic Modulation Spectroscopy (MMS), a powerful new technique that securely identifies conformational instability and aggregation by sensitively detecting changes in intermolecular beta sheet structure. The benefits of MMS relative to conventional FTIR spectroscopy are illustrated via experimental data.