T H E USE OF ADJUVANTS IN STUDIES ON INFLUENZA IMMUNIZATION I. MEASUREMENTS IN MONKEYS OF THE DIME.NSlONS OF ANTIGENICITY OF VIRus-MINERAL OIL EMULSIONS* Bx

Rather early in studies on influenza immunization in animals as well as in man, it was realized that immunizing effect, as reflected in antibody response induced by the vaccines employed, was limited and of relatively short duration. For these reasons (1) a variety of methods were explored for enhancing and prolonging the protective effect induced by vaccination (2-7). None, however, provided such striking results as those obtained in studies in animals reported by Friedewald (6), and in studies in man reported by Henle and Henle (7). These investigators used vaccines consisting of virus in water-in-oil emulsions in the manner developed in recent years by Freund (8). Although the immunologic data derived by Friedewald and the Henles were outstanding, in comparison to the effects induced by vaccines consisting of virus in an aqueous medium alone, the immunologic success was blighted by the occurrence of undesirable reactions at the site of inoculation. The problem remaining after these experiences seemed merely to be one of reducing or eliminating the untoward local reaction while retaining the immunologic advantage. That this could be accomplished was evident from observations made, in the course of certain other studies (9), when it was found that rather large doses of water-in-oil emulsions without acid-fast bacilli could be inoculated into monkeys without untoward local reactions. In the studies referred to reagents were used which were different from those employed by Friedewald and the Henles and the inoculum was introduced intramuscularly rather than subcutaneously. When influenza virus vaccine was prepared in this particular water-in-oil emulsion and administered to monkeys intramuscularly, it too could be given without producing undesirable effects at the inoculation site.