New Research on Influenza: Studies with Normal Volunteers

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Abstract
A possible role for equine influenza (A/equine-2/Miami/63) in human illness was suggested by the finding that 5 human volunteers became infected and one became ill with influenza following inoculation with this equine strain. Other studies revealed that successful initiation of influenza infection in volunteers requires avoidance of egg passage of the inoculum, relative or complete lack of antibody to the inoculating strain, and an adequate dose of inoculating virus. Illness and virus infection occurred uniformly in 19 volunteers in whom these factors were controlled. Nasal instillation of a killed preparation of PR8 influenza virus failed to prevent later infection with A1/Japan/305/57 in 4 subjects, although the febrile response associated with the infection appeared to be somewhat less than in 2 control subjects. This experiment was based on the finding that killed influenza virus stimulated production of interferon in tissue culture. In a study of the effect of pre-existing antibody on susceptibility to infection with influenza, high titers to 3 A2 strains were shown to be associated with immunity. A high proportion of subjects with moderate titers to the 3 strains, however, became infected and ill. Paradoxically, subjects with low titers to the inoculating strain and none to the 2 other strains did not become ill. It was suggested that these volunteers had had recent infection with the homologous strain while antibody in the other subjects had resulted from infection with other influenza strains. From this, it follows that antibody derived from prior infection with a homologous strain may be more protective than antibody derived from a heterologous strain. This thesis currently rests on assumption, however, because conventional serologic tests do not discriminate between antibody which results from antigens shared by influenza strains within a virus group and true homologous antibody.