Treatment of influenza virus-infected SCID mice with nonneutralizing antibodies specific for the transmembrane proteins matrix 2 and neuraminidase reduces the pulmonary virus titer but fails to clear the infection

Antibodies (Abs) can contribute to the cure of a viral infection, in princi ple, in two ways by: (1) binding to infected cells and thereby reducing the production of progeny virus [here termed cell-targeting (CT) activity] and (2) reacting with released progeny virus and thereby inhibiting the spread of the infection [termed virus neutralizing (VN) activity]. We have previo usly shown that a pulmonary influenza virus infection in severe combined im munodeficient mice could be cured by treatment of these mice with hemagglut inin (HA)-specific monoclonal Abs (mAbs) that mediated both of the above ac tivities. Although the therapeutic activity of these mAbs correlated with t heir VN activity, it remained unclear how much their CT activity contribute d to the Ab-mediated recovery process. To clarify this point, we tested the therapeutic efficacy of two mAbs of IgG2a isotype that mediated CT but no VN activity: one specific for the viral neuraminidase and the other for mat rix protein 2. Both mAbs reduced pulmonary virus titers by 100- to 1000-fol d but they failed to clear the infection, even when administered in combina tion and at therapeutically saturating concentrations;The results suggest t hat CT activity contributes significantly also to the therapeutic activity of HA-specific mAbs and further support the notion that VN-activity is requ ired for Ab-mediated virus clearance. (C) 1999 Academic Press.