Kinetics and specificity of orthoflaviviruses NS1 IgG after Zika virus infection in Yellow fever and dengue immunized individuals: a memory recall hypothesis

Pre-existing Orthoflavivirus immunity can shape antibody recall upon infection with a heterologous virus. We monitored Zika virus (ZIKV) infection in individuals vaccinated against yellow fever virus (YFV), with or without prior dengue virus (DENV) exposure. We obtained longitudinal serology data (NS1- and whole-virus IgG responses) and neutralization titers on days 0 and 28 after ZIKV infection. YFV-neutralizing antibody levels remained stable over time, consistent with the long-lasting immunity induced by YFV vaccination. By contrast, ZIKV infection triggered an increase in anti-YFV NS1 IgG, suggesting a selective recall of YFV-specific memory B cells. A similar trend was observed for anti-DENV NS1 IgG exclusively in DENV-immune individuals. Thus, prior Orthoflavivirus exposure shapes the specificity and magnitude of NS1-directed humoral recall, with implications for serological interpretation.