Two outcomes of antibody binding
Neutralizing antibody
- Binds receptor-binding site or fusion machinery
- Blocks attachment or prevents the conformational change needed for fusion
- Prevents infection directly, without needing other cells
- Targets are typically the surface proteins required for entry
Non-neutralizing antibody
- Binds epitopes not required for entry, or binds at low density
- Does not prevent the virion from infecting a cell
- Contributes through Fc-mediated effector functions: complement, phagocytosis, ADCC
- Can dominate a binding assay while providing limited protection
Why the target determines the outcome
Neutralization depends on where the antibody binds, not simply on how tightly it binds. An epitope that sits on the receptor-binding surface or on a fusion loop is functionally essential, so occupying it blocks entry. An epitope on an internal or dispensable region can be bound without consequence. This is why antibody titers measured by simple binding assays do not always predict protection, and why vaccine design focuses on presenting the entry machinery in its vulnerable conformation.
The Fc region is not decoration
The Fab arms determine what the antibody binds; the Fc region determines what happens after binding. Fc engagement of complement and Fc receptors can clear virions and infected cells even when neutralization is weak, so antibody-mediated protection is the sum of neutralization and effector function.