Professor Graz University of Technology Graz, Austria
This presentation focuses on the use of preformulation characterization of new vaccine candidates as a core formulation development activity. Goals include identifying key structural attributes (physicochemical and immunological), determining degradation pathways, and selecting stability-indicating analytical methods to develop stable vaccine formulations suitable for clinical use. An emphasis on low-cost vaccine formulations leads to unique stability challenges including: (1) the presence of adjuvants to boost immunogenicity and reduce antigen dose, (2) the addition of preservatives to enable multidose formulations, (3) the combination of multiple antigens into a single dosage form, and (4) the use of non-parenteral routes of administration (without expensive delivery technologies).
These points are illustrated with three recent case studies with new rotavirus vaccine candidates targeted for use in low- and middle- income countries. First, formulation challenges with a live, attenuated viral vaccine candidate (RV3-BB currently in mid-stage clinical trials) are presented including improving storage stability and providing sufficient acid-neutralizing capacity to enable oral administration without the need for preneutralization of gastric acid. Second, ongoing formulation development of a non-replicating rotavirus vaccine (NRRV) candidate (three recombinant fusion-protein antigens) for use in late-stage clinical trials in Africa is presented. Third, challenges and opportunities in designing recombinant protein vaccine antigens with optimal molecular properties to enable low-cost production in low-cost formulations are discussed in the context of NRRV antigens formulated with aluminum adjuvant and preservatives.