Development of Biophysical Assays to Better Understand Adjuvanted Vaccine Formulation Potency and Stability

The essential requirements that a vaccine be safe and efficacious can be restated as a formulation that it is made with the appropriate potency that persists over the duration of conditions until it is administered to the patient [1–3]. When a vaccine elicits an immune response of sufficient valence and strength to induce protection against a pathogenic threat without unacceptable adverse effects and the critical biomolecular factors contributing to that response are well defined and characterized, the formulation can be reliably given with a strong assurance of both safety and efficacy. Historically such tests for potency have been functional assays such as infectivity titers and in vivo induction of antibodies [4–8], though these tests are generally time and resource intensive; more importantly, they are “black box,” empirical verification that whatever was tested either worked or didn’t, offering little insight into why the system behaved as it did, and how it could be improved if desired. When a rapid response is needed such as production and distribution to combat an emerging pandemic, such tests are often unfeasible or untimely, as the case of the recent H1N1 flu pandemic demonstrated [9, 10], when several batches of influenza vaccine were produced, shipped, and administered to patients before it was determined the vaccine potency had dropped below specified levels. There is considerable effort and potential reward in both time and cost savings to develop in vitro tests that show correlation to in vivo potency [11–19]. With increased experimental understanding of structural immunology, it may become possible to establish a set of specifications that establish vaccine performance based upon higher order structures, i.e. biophysical critical quality attributes as described in ICH Q6b [20, 21].