Prepandemic influenza vaccine H5N1 (split virion, inactivated, adjuvanted) [Prepandrix (TM)] - A review of its use as an active immunization against influenza A subtype H5N1 virus

Although rare, influenza pandemics are a recurrent event, and influenza A/H5N1 is generally considered to be the most likely causative agent of the next pandemic. Vaccines are widely considered to be the first line of defense for protecting populations in advance of an influenza pandemic. Because it is not known beforehand which strain of influenza A/H5N1 virus could give rise to a pandemic, prepandemic vaccines that impart broad cross-reactive immunogenicity are required. In addition, low doses of H5 hemagglutinin are preferable in order to make antigen supplies go further towards meeting global demands for prepandemic vaccines. Prepandemic influenza vaccine H5N1 [Prepandrix (TM); AS03-H5N1 vaccine] is a split virion, inactivated vaccine containing H5 hemagglutinin antigen adjuvanted with a novel 10% oil-in-water emulsion-based adjuvant system (AS03). It is approved in the EU for use as an active immunization against H5N1 subtype influenza A virus (influenza A/H5N1 virus) in adults aged 18-60 years. The recommended dosage in this population is two doses of 0.5 mL containing 3.75 mu g of H5 hemagglutinin, administered >= 21 days apart. Adjuvantation of H5N1 vaccine with AS03 allows for a reduction in the H5 hemagglutinin dose required to elicit an adequate immune response, and administration of two doses of the adjuvanted vaccine met all criteria for the licensure of influenza vaccines set out in European Committee for Proprietary Medicinal Products (CPMP) and US FDA documents. In two clinical trials, two doses of AS03-H5N1 vaccine containing 3.75 mu g of H5 hemagglutinin induced an immune response in healthy volunteers aged 18-60 years against the homologous, clade 1 vaccine strain, A/ Vietnam/1194/2004, and the heterologous, drifted, clade 2 nonvaccine strains, A/Anhui/1/2005, A/Indonesia/5/ 2005, and A/turkey/Turkey/1/2005. This cross-clade response persisted for >= 6 months following administration of the first vaccine dose in the majority of vaccine recipients. In addition, AS03-H5N1 vaccine protected against lethal challenge with A/Vietnam/1194/2004 or A/Indonesia/5/2005 in animal studies. The vaccine was generally well tolerated and adverse events were transient and predominantly of mild to moderate severity. AS03-H5N1 vaccine has demonstrated antigen dose-sparing properties and cross-clade reactive immunity in clinical trials and challenge studies in animal models. As a result, stockpiling AS03-H5N1 vaccine has the potential to protect populations against a pandemic caused by an influenza A/H5N1 virus and may represent an important measure in pandemic preparedness.