The Recall Phenomenon in the Antibody Response to Influenza Vaccines

Orientation of the antibody response to influenza viruses by previous experience has been studied by several different approaches utilizing hemagglutination-inhibition tests (21–26). With this technique of antibody measurement, the data presented in this report afford primarily a confirmation of the earlier findings by an additional study design. Orientation of antibody response in terms of the complement fixation reaction appears to be a new finding, even by the indirect method presented here. Indeed, in this study, the demonstration of strain specific reactivity of human sera seemed dependent upon the accentuating effect of prior antigenic experience. In addition, had not the distantly related PR-8 virus been used to measure the complement fixing antibody response to an A′ vaccine, the evidence for a “recall response” would have been rather unconvincing. In contrast, the effect of prior antigenic experience could be demonstrated with relative ease by hemagglutination inhibition tests with the much more closely related FM-1 and Cuppett strains; the highly strain specific reactivities of this technique presented difficulties in detecting a “recall phenomenon” with strains which are widely divergent antigenically, e.g., PR-8 and FM-1. It has been previously noted (15–17) that allantoic fluids used as complement fixing antigens possess strain specific reactivities. Extensions of these studies, by Hoyle (18) and by Lief and Henle (19, 20), have further indicated that S antigens can be obtained in essentially pure form by means of simple differential centrifugation and adsorption techniques, and that these S antigens are type specific rather than strain specific. Even in the most purified preparations (19, 20), V antigens entirely free of S are not as yet available, and it appears that material with S reactivities forms an integral part of the influenza virus particle. In practice, V antigens actually represent a mixture of viral and soluble antigens. It seems reasonable to believe, therefore, that if a very highly purified viral antigen were utilized in contrast to the crude antigen employed in these studies, strain specific reactivity and the orientative effect of prior antigenic experience might be more readily demonstable.