Assessment of resistance to influenza virus infection in animal models

The antibody response and immunity to challenge infection were determined in ferrets immunized with inactivated influenza vaccine in saline or adjuvant. Adjuvanated vaccines induced variable titres of serum antibody, and the degree of immunity to challenge infection was directly related to the titre of serum HI antibody induced by these vaccines. Conventional doses of saline vaccine did not induce serum HI antibody, and the ferrets were completely susceptible to challenge infection. Infection with live virus produced a more solid immunity to challenge infection than immunization with a adjuvant vaccines, even though immunization induced higher titres of serum HI antibody. Ferrets previously infected with a heterotypic influenza A virus, but not other viruses, produced serum HI antibody in response to subsequent immunization with inactivated influenza vaccine. Similar results were obtained in hamsters and mice. Thus, the failure of animals to produce antibody in response to immunization with saline inactivated vaccines was due to the absence of a previous priming infection; this prior experience would be a feature of most volunteers. Live virus infection produced nasal antibody in ferrets, but inactivated vaccines only induced serum antibody. This may explain the more solid immunity observed following infection; however, at the time of challenge infection, no nasal wash antibody could be detected. Immunization with inactivated vaccine in Freund's complete adjuvant and influenza virus infection both produced a cell-mediated immune response; thus, the difference in the degree of immunity induced by these two immunization procedures are probably not due to differences in the cell-mediated immune response. However, cell-mediated immunity was measured by skin tests and by macrophage migration inhibition tests with spleen cells; the reaction of cells from the respiratory tract may be more important, but was not measured in these studies.