Development of a protein microarray for analysis of humoral immune responses to flavivirus infection and vaccination

Abstract

Dengue virus (DENV), yellow fever virus (YFV), West Nile virus (WNV), and Zika virus (ZIKV) are the leading causes of mosquito-borne human flavivirus infections in the Americas. Serological assays for diagnosis and surveillance are generally directed towards one specific virus and disregard the potential for antibody cross reactivity between nearest neighbors. Here, a comprehensive assay was developed that included whole virus preparations and recombinant antigens from 15 human pathogenic flaviviruses. Using the printed microarrays, serological immune responses to ZIKV, WNV, DENV, and YFV infections of humans and nonhuman primates (NHPs) were examined in order to examine specificity and cross reactivity of antibody responses among the viral antigens. Sera were further employed from yellow fever vaccine studies to demonstrate the utility of using multiple viral antigens for obtaining a detailed analysis of antibody responses to vaccination. Results from the microarray assays indicated that antibody recognition of isolated flaviviral antigens can be used to resolve complex infection histories, as well as provide a detailed understanding of immune responses to YFV vaccination in areas of flavivirus endemicity.