FIG 4.

Theoretical mechanism for anti-HA antibody mediated NI activity. (A) Anti-NA antibodies are able to result in NI activity by directly binding to and blocking the enzymatic active site of the NA. (B and C) However, it is conceivable that antibodies against the HA head and stalk domain may, by steric hindrance, shield the NA active site from the substrate. Because stalk-directed MAbs bind lower on the HA glycoprotein, this steric hindrance effect may not be as robust (C), possibly explaining the lower NI seen with 9H10 in Fig. 3. (D) This scenario may be further complicated by the HA/NA ratio, extent of NA clustering on the virus surface, differences in specific NA activity and differences in strengths and kinetics of individual MAb binding profiles. Detergent treatment (Triton X-100) of the virus releases HA and NA from the viral membrane and disassociates them from each other. Both HA head and stalk MAbs lost all NI activity under these conditions, while the NA antibody retained its activity.