LB18. Understanding Zika-Specific Immunity for Prevention and Protection

Abstract

Background. Flavivirus infection represents a major public health problem, with over 2 billion people at risk for one or more infections each year. There are no licensed antiviral treatments for flaviviruses, and effective vaccines are lacking for several. Accurate diagnosis of flaviviruses is also complicated by serologic cross-reactivity. Thus, there is an urgent need to develop public health tools and interventions to reduce the burden of flavivirus infection worldwide. Methods. We recently isolated two potently neutralizing human monoclonal antibodies (NmAb) against Zika, which exhibit activity against multiple strains of Zika but do not bind the closely related dengue virus. Mapping studies revealed that the NmAb target distinct epitopes on the envelope protein (E). A competition ELISA (ZE-BOB) was developed with the two NmAb to test the hypotheses that neutralizing Ab responses in the general population would target the same epitopes on Zika E as the novel NmAb. Results. We found that competitive Ab responses were detected in 19 of 19 (100%) convalescent sera from travelers with confirmed Zika infection. We tested a panel of 20 sera from individuals with either primary or secondary prior dengue infection and found that 18/20 (90%) contained IgG reactive with Zika virus; however, 0/20 (0%) exhibited ZE-BOB activity. These results indicate that the epitopes targeted by these two Zika NmAb are consistently immunogenic humans infected by Zika. Additionally, these epitopes elicit type-specific Ab to Zika, providing a basis for development of simple serodiagnostic assays with utility in epidemiologic studies as well as in the clinical setting. Because NAb are key determinants of long-term protection against future flavivirus infection, we further hypothesized that the results of the ZE-BOB assay may simultaneously provide a correlate of immunity, which would be a critical tool for vaccine development. In comparing the 50% neutralization titer against Zika with the magnitude of competition by ZE-BOB, there was no correlation in these values, but sera tended to be positive in both or neither assay. Conclusion. Therefore, the ZE-BOB assay constitutes a novel tool that is widely deployable for purposes ranging from clinical diagnosis to epidemiologic monitoring to vaccine development for Zika. (Figure Presented).