The association of enhancing antibodies with seroconversion in humans receiving a dengue-2 live-virus vaccine.

A group of human subjects, some with yellow fever (YF) antibodies, volunteered for testing of a live-attenuated dengue-2 (DEN-2) vaccine. Serum samples taken before DEN-2 vaccination were tested for their ability to enhance infection of human monocytes by DEN-2 virus. A significantly greater proportion of enhancing antibodies (Eab) were found in YF-immune (YFI) individuals (50%) as compared to those with no evidence of flavivirus infection (9.5%). Geometric mean titers of neutralizing and hemagglutination inhibiting antibodies to DEN-2 virus in YFI subjects with Eab were fourfold to seven-fold higher than in the YFI subjects without Eab in prevaccine sera and 10- to 35-fold higher than in non-immune volunteers. Additionally, levels of Eab in prevaccine sera were directly related to antibody titers found in postvaccine sera. The presence of Eab in the serum of a human subject before DEN-2 vaccination was a good predictor of the immune response after vaccination, and may in part be responsible for the higher seroconversion rate in YF immunes (90%) as compared to nonimmunes (61%) receiving this vaccine. This is the first human study to demonstrate that circulating Eab in non-DEN-immune persons is associated with an augmented immune response to DEN virus infection. This finding supports the hypothesis that cross-reactive antibodies against one flavivirus enhance an infection with another closely related flavivirus.