Correlation between the reactivity patterns of monoclonal antibodies to distinct antigenic sites on HN glycoprotein and their protective abilities in Sendai (6/94) virus infection

The relative importance of the host immune response to various antigenic and functional sites on the HN glycoprotein of Sendai (6/94) virus for protection in vivo, was evaluated in mice passively immunized with monoclonal antibodies to HN and then intranasally challenged with infectious virus. Five neutralizing monoclonal antibodies reacting with distinct antigenic sites and exhibiting different reactivity patterns were selected. All of them were able to prevent entirely the growth of virus in the lungs of experimental animals injected with appropriate dilutions of monoclonal antibody. The calculation of correlation coefficients between the reduction of virus in the lungs of immunized mice and the amount of antibody, expressed in terms of hemagglutination inhibition, hemolysis inhibition or neutralizing units, showed a high degree of correlation (r = 0.89) with neutralization and a lack of correlation (r = 0.44) with hemagglutination inhibition. In parallel a minimum threshold value for protection equivalent to 2 x 10(3) neutralizing units per mouse was determined independently of the mechanism(s) by which monoclonal antibodies mediated the neutralization of the infectivity. On the HN glycoprotein of Sendai (6/94) virus we could not individualize a critical site for successful immune recognition by antibodies although the characteristics of an "ideal protective monoclonal antibody" have also been defined.