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

J Pharm Sci. 2011 Apr;100(4):1436-43. doi: 10.1002/jps.22367. Epub 2010 Oct 19.

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.

Keywords: biodegradable polymers vaccine delivery; polyelectrolytes; polymeric drug delivery systems; stabilization; vaccine adjuvants.

MeSH terms

  • Adjuvants, Immunologic / chemistry
  • Adjuvants, Immunologic / pharmacology*
  • Animals
  • Excipients / chemistry
  • Excipients / pharmacology*
  • Ferrets / virology
  • Humans
  • Influenza A Virus, H5N1 Subtype / immunology*
  • Influenza Vaccines / chemistry
  • Influenza Vaccines / immunology
  • Influenza Vaccines / pharmacology*
  • Organophosphorus Compounds / chemistry
  • Organophosphorus Compounds / pharmacology*
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / prevention & control*
  • Polymers / chemistry
  • Polymers / pharmacology*

Substances

  • Adjuvants, Immunologic
  • Excipients
  • Influenza Vaccines
  • Organophosphorus Compounds
  • Polymers
  • poly(di(carboxylatophenoxy)phosphazene)