Dengue Virus (DV) enhancing antibody activity in preillness plasma does not predict subsequent disease severity or viremia in secondary DV infection

Abstract

BACKGROUND: Dengue hemorrhagic fever, the most severe form of dengue illness, is associated with secondary dengue virus (DV) infection. Preexisting nonneutralizing antibodies to DV that enhance the infection of Fc gamma receptor-bearing cells have been implicated in DV pathogenesis. METHODS: We conducted a prospective cohort study in Thai schoolchildren. Enhancing activity (EA) was measured as the percentage of DV-infected K562 cells, and viral titer (infected K562 cell supernatants) was measured in preillness plasma samples from children who subsequently had secondary DV2 or DV3 infection. RESULTS: Plaque-reduction neutralizing titers to the child's own DV2 or DV3 isolate were detected in 23 of 32 and 8 of 27 of the preillness plasma samples, and EA was detected to a low-passage Thai DV2 or DV3 in 31 of 32 and 26 of 27, respectively, of the samples. EA in undiluted preillness plasma did not correlate with subsequent disease severity or peak viremia levels in either secondary DV2 or DV3 infections. CONCLUSIONS: Preillness plasma enhances DV infection of K562 cells even in the presence of detectable neutralizing antibodies in LLC-MK2 cells. However, levels of preillness plasma EA of DV infection in K562 cells did not correlate with the clinical severity or viral burden of secondary DV infection.