Seasonal influenza constitutes a significant healthcare problem in the U.S., with an estimated 17 to 50 million persons affected yearly. Influenza was responsible for an average of 36,000 deaths annually throughout the decade 1990-1999. Elderly patients are at particular risk, accounting for 80-90% of influenza related deaths. In the US, the economic cost of the annual flu season is estimated at $ 71-167 billion. The principal means of preventing influenza is by immunization with seasonal influenza vaccine. Influenza vaccination, which has efficacy rates from 70-90% in young adults, is effective in only 27-75% in elderly subjects. A vaccine that increases efficacy in the elderly would be of significant benefit. In addition, influenza vaccine with greater immunopotency than the present vaccine would have a significant beneficial impact where vaccine supplies were scarce, such as for emerging strains of influenza virus or for shortfalls in manufacture of seasonal vaccine stocks. Such a dose-sparing effect would stretch vaccine stocks to help ensure sufficient supplies to protect the U.S. population. Moreover, the enhanced immunopotency could have an epitope spreading effect, where antibodies are produced against less dominant epitopes, thereby increasing the possibility of cross reactivity with other strains of influenza virus. The objective of this program is to develop a prophylactic influenza vaccine to help fulfill these needs. The approach combines a potent new adjuvant, MAS-1, which has an established safety record from over 20 clinical trials, with approved seasonal influenza vaccine antigens. MAS-1 is advantageous in that it can be formulated to cGMP by a fully validated process in a licensed facility on a large scale adequate for prophylactic vaccines or it can be formulated at the clinic with pre-distributed MAS-1 adjuvant vehicle and standard influenza vaccine antigens by a validated point-of-use mixing method. Both formulation methodologies will be assessed with seasonal influenza vaccine in this program. The work will include initial formulation testing to confirm mixing parameters for MAS-1 influenza vaccine. This will be followed by proof of concept studies in laboratory animals to demonstrate that MAS-1 enhances the antibody response to the three component strains of virus in the seasonal influenza vaccine, in comparison with standard (non- adjuvanted) vaccine. These studies will include dose ranging to establish effective doses of influenza antigens and of injection volume, and the outcome will be based primarily on the measurement of anti-H antigen antibody titers by the standard hemagglutination inhibition assay. A sub-acute, pre-clinical toxicology study will be performed on the MAS-1 influenza vaccine to confirm safety as a prelude to clinical evaluation. This two year program will culminate in the preparation and filing of an IND for clinical trials of MAS-1 influenza vaccine. ? ? ?
