Development and evaluation of AS03, an Adjuvant System containing α-tocopherol and squalene in an oil-in-water emulsion

Abstract

AS03 is an Adjuvant System composed of α-tocopherol, squalene and polysorbate 80 in an oil-in-water emulsion. In various nonclinical and clinical studies, high levels of antigen-specific antibodies were obtained after administration of an AS03-adjuvanted vaccine, permitting antigen-sparing strategies. AS03 has been shown to enhance the vaccine antigen-specific adaptive response by activating the innate immune system locally and by increasing antigen uptake and presentation in draining lymph nodes, a process that is modulated by the presence of α-tocopherol in AS03. In nonclinical models of the AS03-adjuvanted prepandemic H5N1 influenza vaccine, increased levels of anti-influenza antibody afforded protection against disease and against virus replication of influenza strains homologous and heterologous to the vaccine strain. By incorporating AS03 in the pandemic H1N1/2009 vaccine, vaccine immunogenicity was increased compared with nonadjuvanted H1N1 vaccines. High H1N1/2009/AS03 vaccine effectiveness was demonstrated in several assessments in multiple populations. Altogether, the nonclinical and clinical data illustrate the ability of AS03 to induce superior adaptive responses against the vaccine antigen, principally in terms of antibody levels and immune memory. In general, these results support the concept of Adjuvant Systems as a plausible approach to develop new effective vaccines.

Keywords::

• α-tocopherol
• Adjuvant System
• AS03
• immunostimulant
• infl uenza
• oil-in-water emulsion
• pandemic
• prepandemic
• vaccine

Acknowledgements

The authors thank A Di Pasquale for her critical scientific reviewing of the manuscript. They also thank P Cadot (XpePharma & Science) and M Morgan (4Clinics) for scientific advice and writing assistance and U Krause (GSK) for coordination of the manuscript development.

Financial & competing interests disclosure

N Garçon, D Vaughn and A Didierlaurent are employees of GlaxoSmithKline Biologicals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing assistance was utilized in the production of this manuscript and was funded by GlaxoSmithKline Biologicals. Pandemrix is a trade mark of the GlaxoSmithKline Group of Companies.