Secondly, oil-in-water emulsions improve vaccine responses against seasonal influenza in elderly populations, immunocompromised

patients and children [6]. They can also broaden the immunogenicity of pandemic vaccines as shown by the MF59-induced epitope spreading from HA2 to neuraminidase and HA1, thus providing cross-clade neutralization and potentially improving in vivo protection [7]. Thirdly, the safety profile of oil-in-water emulsions is well documented: MF59 and AS03 have been used successfully in over 100 million people including children. Novartis’ seasonal influenza vaccine containing MF59 is routinely and extensively used in the elderly [8], and both GSK’s AS03-adjuvanted pandemic (H1N1) 2009 influenza vaccine and Novartis’ MF59-adjuvanted pandemic (H1N1) Enzalutamide 2009 influenza vaccine were used worldwide in 2009 and 2010. It is worth noting that the technology transfer of an emulsion containing metabolizable oil and surfactant in the absence of block-copolymer from a European centre to DCVMs does not infringe any intellectual property. Access by DCVMs to this adjuvant technology would therefore be highly advantageous not only

for pandemic influenza vaccines, but could trigger benefits for further applications since oil-in-water emulsions have been widely investigated in numerous clinical trials with several subunit antigens, such as HIV, hepatitis B virus and hepatitis C virus Libraries antigens LY2157299 price [9]. In addition, the capital investment needed to produce oil-in-water

adjuvants is relatively modest and the cost of materials adds only marginally below to the cost of antigen production. The manufacturing process for oil-in-water emulsions has been described in detail [10]. The Vaccine Formulation Laboratory has established the production processes and prepared oil-in-water emulsions that meet all expected physical, chemical and biological (adjuvant activity) parameters. We are currently screening a range of raw material sources and evaluating the acceptability of the products for use in clinical-grade emulsions. This is particularly important for materials of biological origin such as squalene (prepared from shark liver) and heterogeneous surfactants such as Tween80 and Span85. In order to develop all standard operating procedures and relevant documentation for Good Manufacturing Practice (GMP) production, a collaboration has been developed with The Netherlands Vaccine Institute (NVI) in Bilthoven, The Netherlands. Bio Farma, Indonesia, a grantee of the WHO initiative to transfer the capacity to produce influenza vaccines to DCVMs, is the first technology transfer partner of the Vaccine Formulation Laboratory. The first phase of the project comprises the installation of equipment required for production and characterization of oil-in-water emulsions, the establishment of relevant standard operating procedures, training of laboratory staff, and on-site validation of the transferred processes.