VARIATIONS IN THE NEUTRALIZING AND HEMAGGLUTINATION-INHIBITING ACTIVITIES OF 5 INFLUENZA-A VIRUS-SPECIFIC IGGS AND THEIR ANTIBODY FRAGMENTS

Neutralization and haemagglutination-inhibition (HI) of a type A influ enza virus by a panel of five monoclonal IgGs, their F(ab')(2)s, Fabs and Fabs+ anti-mouse Fab were compared, The MAbs were specific for ant igenic sites A, B and D of the haemagglutinin. Activities of the IgGs varied by up to 6-fold on a molar basis, apart from the HI activity of HC58 which was > 100-fold lower, This was not due to low functional a ffinity as HC58 had the second highest value (nM) as determined by an equilibrium method with whole virions, Conversion to the F(ab')(2) red uced neutralization and HI by only 2- to 6-fold, indicating that the p c region had little involvement in these processes, However, all Fabs had low neutralization and HI activity compared with their IgGs, neutr alization being reduced by 86 to > 1912-fold, and HI by 13 to > 69-fol d. Although decreased, their affinities remained high, in the nM range , Neutralization and HI by three of the Fabs (HC2, HC3W and HC61) were restored by the addition of anti-fab IgG; however, HC10 Fab+anti-Fab IgG still had no detectable neutralization activity but gave HI, and H C58 Fab+anti-Fab IgG had no detectable HI activity but neutralized to the same extent as its IgG, The different properties of the antibodies are discussed in the light of their known mechanisms of action: HI by steric blocking of attachment of virus to the red cell receptor, and neutralization by the inhibition of post-attachment events (HC2, HC10 and HC61), The data demonstrate just how variable are the antiviral pr operties of individual IgGs.