The lungs of C3H/HeMg mice infected with a lethal dose of the influenza virus A/WSN (H1N1) contained antibody to the viral neuraminidase glycoprotein but not to the haemagglutinin (HA). When coinoculated with a life-saving amount of defective interfering (DI) WSN, lungs were found to contain both anti-neuraminidase and haemagglutination-inhibiting (HI) antibodies which peaked at 3 and 5 days post-infection (p.i.), respectively. Mice coinoculated with WSN and β-propiolactone-inactivated DI WSN had only anti-neuraminidase antibody in the lungs. The HI activity was unusual in that there was no detectable neutralizing activity. The HI activity has been affinity-purified by adsorption to and elution from WSN HA and consisted entirely of IgG, comprising isotypes IgG1, IgG2a and IgG2b. The antibody was specific for WSN HA, of low avidity and had disappeared from the lungs by 20 days p.i. Transfer of affinity-purified HA-specific, non-neutralizing antibody to mice 24 h before infection with WSN alone protected 60% from death. We conclude that the antibody contributes significantly to the life-saving activity of DI WSN virus and that the ability to stimulate such antibody represents a novel property of this DI virus.


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