Assessment of immunity to influenza using artifical challenge of normal volunteers with influenza virus.

The candidate humoral mediators of protection against influenza include antibody (Ab) to the viral hemagglutinin (H) or neuraminidase (N) in serum or respiratory secretions. In the present studies these mediators were evaluated principally by low dose live virus challenge of previously vaccinated volunteers. Following IM vaccination with H3N2 virus, Ab appeared in both serum and secretions and direct quantitative relationship between the two was noted. Among individuals vaccinated intranasally with comparable doses, the serum and secretion Ab responses were similar to those after IM vaccination. Irrespective of immunization method, there was a better correlation between protection and titers of serum Ab than titers of Ab in nasal secretions. After vaccination with an N-specific vaccine, an inverse correlation between titer of serum anti-neuraminidase Ab and quantity of virus in secretions occurred. This was reflected in occurrence of illness in those with low Ab titers, infection only in those with intermediate Av titers and no evidence of infection in those with high Av titers. In a naturally occurring outbreak with the England variant, a similar pattern of infection responses occurred among persons with varying titers of serum anti-hemagglutinin Ab. This suggests that, in man, Ab to the H and to the N results in similar host responses to infection and that the extent of infection is determined by magnitude ofAb present.