The overall objective is to develop a new vaccine approach based on the preparation of anti-Id antibodies able to stimulate the humoral and cellular anti-influenza virus immunity. The major thrust of this proposal is based on our previous studies demonstrating shared idiotopes among antibodies specific for hemagglutinin and neuraminidase of various virus subtypes, among antibodies specific for laboratory induced variants and an interspecies cross-reactive idiotype shared by human and murine anti- PRB antibodies. The proposed study bears upon: 1) Preparation of anti-id antibodies against antibodies specific for laboratory induced variants and studies of their effects on humoral responses and viral replication. 2) Immortalization of human B cell clones producing antibodies specific for the Idx expressed on murine and human anti-PRB antibodies and to determine in vitro which of these antibodies stimulate influenza virus specific clones. 3) Studies of the effects of antibodies on cellular responses and viral replication. The effects of three types of antibodies will be studied a) anti-TCR antibodies, b) a hybrid bifunctional antibody (specific for TCR of CTL and HA of influenza virus) which can efficiently focus CTL on infected target cells. c) a genetically engineered antibody containing an inserted viral epitope. These studies are aimed to determine the enhancing effects of anti-id antibodies on immune reaction against influenza virus, a system in which vaccines produced by classical approaches has not succeed in overcoming epidemics resulting from a high potential for natural antigenic variation of the virus.