Formulation Studies During Preclinical Development of Influenza Hemagglutinin and Virus-Like Particle Vaccine Candidates.

A critical element of vaccine formulation studies is the identification of chemical and physical degradation pathways that compromise structural integrity, and which may in turn affect the clinical safety and efficacy, of macromolecular antigens. Formulation development helps optimize and maintain the long-term storage stability and viability of vaccine antigens in pharmaceutically relevant dosage forms. The protocols presented in this manuscript highlight the use of accelerated stability studies for the formulation of influenza vaccine candidates including virus-like particles (VLP) and particle forming hemagglutinin (HA) antigens. Three case studies, each targeting a different facet of preclinical vaccine formulation development, are reviewed: (1) excipient screening experiments to mitigate VLP physical degradation, (2) methods for monitoring a specific chemical perturbation of the recombinant HA antigen and elucidating its effect on in vitro potency, and (3) maintaining HA conformational stability in the presence of freeze-thaw and freeze-drying stresses.