Zika virus infection in early pregnancy increases the likelihood of persistent neutralizing antibodies

BACKGROUND: Neutralizing antibodies (nAbs) play a central role in protection against Zika virus (ZIKV) infection. Higher maternal ZIKV nAb titers during pregnancy have been associated with reduced risk of congenital anomalies. However, limited data exist on the long-term persistence of these antibodies in women infected during pregnancy and in children exposed in utero. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a cross-sectional serological study using stored serum samples from a cohort of mother-child pairs with confirmed maternal ZIKV infection during pregnancy in Campo Grande, Brazil. ZIKV nAb titers were measured in samples collected approximately 3-4 years after maternal infection using plaque reduction neutralization testing. Among 77 women, 66.2% (51/77) had ZIKV nAbs above the cutoff point, with higher titers observed in patients with first trimester infection. In contrast, only 2 of 72 children (2.8%) presented detectable ZIKV nAbs following clearance of maternal antibodies. No clear association was found between maternal nAb titers and adverse child outcomes. CONCLUSIONS/SIGNIFICANCE: Our findings suggest long-term persistence of neutralizing antibodies in most women infected with ZIKV during pregnancy, especially when infection occurred in the first trimester of pregnancy ZIKV-specific nAb persistence was rare in children with antenatal exposure once maternal antibodies waned, reinforcing concerns about limited postnatal protection in this group. These results underscore the importance of further studies to clarify the role of neutralizing antibodies in long-term protection and disease pathogenesis, particularly in endemic regions where the risk of reinfection or exposure to related arboviruses remains high.