Dengue virus infection-enhancing activity in serum samples with neutralizing activity as determined by using FcγR-expressing cells

Background: progress in dengue vaccine development has been hampered by limited understanding of protective immunity against dengue virus infection. conventional neutralizing antibody titration assays that use fcγr-negative cells do not consider possible infection-enhancement activity. we reasoned that as fcγr-expressing cells are the major target cells of dengue virus,neutralizing antibody titration assays using fcγr-expressing cells that determine the sum of neutralizing and infection-enhancing activity,may better reflect the biological properties of antibodies in vivo. methods and findings: we evaluated serum samples from 80 residents of a dengue endemic country,malaysia,for neutralizing activity,and infection-enhancing activity at 1:10 serum dilution by using fcγr-negative bhk cells and fcγr-expressing bhk cells. the serum samples consisted of a panel of patients with acute denv infection (31%,25/80) and a panel of donors without acute denv infection (69%,55/80). a high proportion of the tested serum samples (75%,60/80) demonstrated denv neutralizing activity (prnt 50≥10) and infection-enhancing activity. eleven of 18 serum samples from patients with acute secondary denv infection demonstrated neutralizing activity to the infecting serotype determined by using fcγr-negative bhk cells (prnt 50≥10),but not when determined by using fcγr-expressing cells. conclusion: human serum samples with low neutralizing activity determined by using fcγr-negative cells showed denv infection-enhancing activity using fcγr-expressing cells,whereas those with high neutralizing activity determined by using fcγr-negative cells demonstrate low or no infection-enhancing activity using fcγr-expressing cells. the results suggest an inverse relationship between neutralizing antibody titer and infection-enhancing activity,and that neutralizing activity determined by using fcγr-expressing cells,and not the activity determined by using fcγr-negative cells,may better reflect protection to denv infection in vivo. © 2012 moi et al.