Differential dengue antibody responses in recipients of a Zika DNA vaccine are governed by dengue immune history

Abstract Dengue virus (DENV 1–4) and Zika (ZIKV) are closely related flaviviruses that induce immunological cross-reactivity. The VRC5283 wild type DNA vaccine is the first to complete a Phase 2b trial (NCT03110770). objective of this study was test if induced potent ZIKV-specific neutralizing antibodies (NAbs) while avoiding priming cross-reactive could potentially enhance dengue disease. Here, we measured NAbs DENV1–4 ZIKV in serum samples obtained from individuals living dengue-endemic (Puerto Rico) non-endemic areas (Texas) immunized with at weeks 0, 4, 8. We performed plaque reduction neutralization tests (PRNT 50) sera collected 0 16 after final vaccination. Sera were tested for isolated Brazil, Sri Lanka. Most had >1:20 prior vaccination, highest NAb titers DENV2. boosted immunity across all cohort, an 8.47-fold increase ZIKV, 2.76-fold DENV1, 1.67-fold DENV3 2.06-fold DENV4 titers, but did not significantly boost DENV2 titers. no or following vaccination observed only ZIKV. Thus, induces immunity. Ongoing testing binding assays will further evaluate whether beneficial enhancing DENV1–4. This work supported by Intramural Research Program NIAID.