Discrepancy in Dengue Virus Neutralizing Antibody Titers between Plaque Reduction Neutralizing Tests with Fcγ Receptor (FcγR)-Negative and FcγR-Expressing BHK-21 Cells

Protective immunity against dengue virus (DENV) is best reflected by the presence of neutralizing antibodies. The conventional plaque reduction neutralizing test (PRNT) is performed using Fc gamma receptor (Fc gamma R)-negative cells. Because Fc gamma R plays a key role in antibody-dependent enhancement, we examined neutralizing antibody titers of mouse monoclonal antibodies and human serum samples in PRNTs using Fc gamma RIIA-negative and Fc gamma RIIA-expressing BHK cells. There was a discrepancy in dengue virus neutralizing antibody titers between PRNTs using Fc gamma RIIA-negative versus Fc gamma RIIA-expressing BHK cells. Neutralizing antibody titers to DENV-1 and DENV-2 tested with monoclonal antibodies, and with most of the human serum samples, were higher in assays using BHK cells than those using Fc gamma RIIA-expressing BHK cells. The results suggest that neutralizing antibody titers determined using Fc gamma RIIA-expressing cells may better reflect the protective capacity of anti-DENV antibodies, as the major target cells of DENV infection are Fc gamma R-positive cells.