Figure 1.

Mechanisms of action of NA-specific antibodies

(A) Current influenza virus vaccine development is focused on trimeric hemagglutinin (HA), the major viral surface glycoprotein important for virus binding to the viral entry receptor, sialic acid (SA). However, tetrameric neuraminidase (NA), the second viral surface glycoprotein, important for releasing virus from SA through its sialidase activity, is reemerging as a potential target. (B) Anti-NA Abs act to antagonize the virus by (1) blocking NA-mediated enzymatic cleavage of virus from mucins in the airway, (2) indirectly blocking HA binding to SA through steric hindrance, (3) acting synergistically with HA stalk Abs to activate FcγR effector functions, such as antibody-dependent cellular cytotoxicity (ADCC), and (4) blocking NA enzymatic activity at the point of viral egress to prevent cleavage of viral aggregates or inhibit viral release and onward spread within the host. Figure created with BioRender.com.