[PDF][PDF] The stoichiometry of antibody-mediated neutralization and enhancement of West Nile virus infection

TC Pierson, Q Xu, S Nelson, T Oliphant, GE Nybakken… - Cell host & …, 2007 - cell.com
TC Pierson, Q Xu, S Nelson, T Oliphant, GE Nybakken, DH Fremont, MS Diamond
Cell host & microbe, 2007cell.com
Antibody binding to the icosahedral arrangement of envelope proteins on the surface of
flaviviruses can result in neutralization or enhancement of infection. We evaluated how
many antibodies must bind to a given epitope on West Nile virus (WNV) to achieve
neutralization. The most potent monoclonal antibodies (mAbs) block infection at
concentrations that result in low occupancy of accessible sites on the virion, with
neutralization occurring when as few as 30 of 180 envelope proteins are bound. In contrast …
Summary
Antibody binding to the icosahedral arrangement of envelope proteins on the surface of flaviviruses can result in neutralization or enhancement of infection. We evaluated how many antibodies must bind to a given epitope on West Nile virus (WNV) to achieve neutralization. The most potent monoclonal antibodies (mAbs) block infection at concentrations that result in low occupancy of accessible sites on the virion, with neutralization occurring when as few as 30 of 180 envelope proteins are bound. In contrast, weakly neutralizing mAbs recognize fewer sites on the virion and require almost complete occupancy to inhibit WNV infection. For all mAbs studied, enhancement of infection is possible in cells bearing activating Fc-γ receptors when the number of mAbs docked to the virion is not sufficient for neutralization. Thus, neutralization is best described by a model requiring "multiple hits" with the cumulative functional outcome determined by interplay between antibody affinity and epitope accessibility.
cell.com