PCPP-formulated H5N1 influenza vaccine displays improved stability and dose-sparing effect in lethal challenge studies

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Abstract

The potential impact of an influenza pandemic can be mitigated through the realization of a successful vaccination program. The implementation of antigen stabilization and dose-sparing technologies is an important step in improving availability of vaccines at the time of a pandemic outbreak. We investigated poly[di(carboxylatophenoxy)phosphazene] (PCPP) as a potential stabilizing and immunostimulating agent for H5N1 influenza vaccine. Physicochemical characterization of PCPP-formulated H5N1 influenza vaccine revealed macromolecular complexation in the system, whereas single radial immunodiffusion assay verified antigenicity of the formulation in vitro. PCPP-enhanced formulation displayed a fourfold increase in the half-life at 40°C compared with a nonadjuvanted vaccine. Lethal challenge studies in ferrets demonstrated 100% protection for low-antigen dose PCPP-adjuvanted formulations (1 μg of hemagglutinin) and at least a 10-fold antigen-sparing effect. Therefore, PCPP demonstrated an ability to improve thermal stability of H5N1 influenza vaccine in solutions and provide for a substantial dose-sparing effect in vivo. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:1436–1443, 2011

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