ZIKA Virus Neutralizing Antibody Kinetics in Antenatally Exposed Infants

Abstract

Background: Zika virus (ZIKV) is associated with severe congenital abnormalities and laboratory diagnosis of antenatal infection is difficult. Here we evaluated ZIKV neutralizing antibody (nAb) kinetics in infants born to mothers with PCR-confirmed ZIKV infection during pregnancy.

Methods: Neonates (n = 98) had serum specimens tested repeatedly for ZIKV nAb over the first 2 years of life using virus neutralization test (VNT). ZIKV neonatal infection was confirmed by RT-PCR in blood or urine and/or presence of ZIKV IgM antibodies, and results were correlated with infant clinical features.

Results: Postnatal laboratory evidence of ZIKV vertical transmission was obtained for 60.2% of children, while 32.7% exhibited clinical abnormalities. Congenital abnormalities were found in 37.3% of children with confirmed ZIKV infection and 31.0% of children without confirmed infection (P = .734). All but 1 child displayed a physiologic decline in ZIKV nAb, reflecting maternal antibody decay, despite an early ZIKV-IgM response in one-third of infants.

Conclusions: Infants with antenatal ZIKV exposure do not develop ZIKV nAb despite an early IgM response. Therefore, ZIKV VNT in children is not useful for diagnosis of congenital infection. In light of these findings, it remains to be determined if children infected in utero are potentially susceptible to reinfection.

Keywords: Zika virus; biomarker; infection status; neutralizing antibodies; vertical transmission.

Figure 1.

Serum ZIKV nAb titers over time in infants born to women with laboratory-confirmed infection during pregnancy. Titers were determined in consecutive serum samples by the virus neutralization test, and log₂ values are shown. Fitted lines represents the polynomial regression (lowess) of (A) all measures (n = 98); (B) cases stratified by the confirmation of Zika infection only by detection of ZIKV IgM (green, n = 14), ZIKV RNA in blood and/or urine (blue, n = 27), or both ZIKV IgM and ZIKV RNA (purple, n = 18), or without confirmation of infection (red, n = 39); and (C) cases stratified by the gestational age at infection, occurring in the first trimester (up to 13 weeks, red, n = 33), in the second trimester (from 14 to 26 weeks, green, n = 45), or during the third trimester (after 27 weeks, blue, n = 20). Abbreviations: nAb, neutralizing antibodies; ZIKV, Zika virus.

Figure 2.

Maternal anti-ZIKV nAb titers in the serum of infants born to women with confirmed infection in pregnancy. A, Anti-ZIKV nAb titers in infants according to age at the time of sample collection, analyzed by Dunn test. Differences in nAb titers in the first 3 months and between 3 to 6 months of life evaluated according to (B) the presence or absence of ZIKV IgM, and (C) the confirmation of Zika infection (ZIKV+). D, ZIKV nAb titers in the first 6 months of life evaluated according to the gestational age at the time of Zika infection. Statistical analysis was performed with Mann-Whitney test. Log₂ titers are shown. Bars represent median values with interquartile range. Abbreviations: nAb, neutralizing antibodies; ZIKV, Zika virus.