PCPP-formulated H5N1 influenza vaccine displays improved stability and dose-sparing effect in lethal challenge studies.
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.
Andrianov
Alexander K
AK
Apogee Technology, Inc., Norwood, Massachusetts 02062. aandrianov@apogeebio.com.
Decollibus
Daniel P
DP
Marin
Alexander
A
Webb
Ashley
A
Griffin
Yolanda
Y
Webby
Richard J
RJ
D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D005079:Excipients / Q000737:chemistry / Q000494:pharmacology*; D005289:Ferrets / Q000821:virology; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000494:pharmacology*; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D005079:Excipients; D007252:Influenza Vaccines; D009943:Organophosphorus Compounds; D011108:Polymers; C546078:poly(di(carboxylatophenoxy)phosphazene)