Castro-Trujillo Sebastián, Mejía William R, Segura Katherine, Castro-Meneses Juanita, Vega Rocío, Salgado Doris, Fonseca Carlos E, Ortiz Ángela M, Perdomo-Celis Federico, Bosch Irene, Narváez Carlos F
División de Inmunología, Programa de Medicina, Facultad de Ciencias de la Salud, Universidad Surcolombiana, Neiva, Huila, Colombia.
Área de Pediatría, Departamento de Ciencias Clínicas, Facultad de Ciencias de la Salud, Universidad Surcolombiana, Neiva, Huila, Colombia.
PLoS Negl Trop Dis. 2025 Jan 6;19(1):e0012193. doi: 10.1371/journal.pntd.0012193. eCollection 2025 Jan.
Gestational Zika virus (ZIKV) infection is associated with the development of congenital Zika syndrome (CZS), which includes microcephaly and fetal demise. The magnitude and quality of orthoflavivirus-specific humoral immunity have been previously linked to the development of CZS. However, the role of ZIKV NS1-specific humoral immunity in mothers and children with prenatal ZIKV exposure and CZS remains undefined. In addition, considering that most of the at-risk population lives in dengue virus (DENV)-endemic areas, it is not clear what is the association between pre-existing DENV NS1-specific humoral immunity and CZS.
Here, we studied 328 mothers and children with a clinical diagnosis and seropositivity for ZIKV infection during pregnancy, included during the 2015-2016 ZIKV epidemic in Colombia. We also performed clinical evaluation and pediatric neurological follow-up. The relative levels of circulating NS1-specific IgM and IgG against ZIKV and DENV were evaluated in mothers and children, and the association with the development of microcephaly was analyzed.
DENV and ZIKV IgG-NS1 antibodies in pregnant women were placentally transferred, and this passage and its duration in children depended on the maternal levels of the antibodies. We reported that higher concentrations of pre-existing DENV, but not ZIKV IgG-NS1 antibodies, were associated with a reduced risk of CZS-related microcephaly. Also, we observed that the IgM-NS1 response in infants is long-term and has a minor association with poor outcomes.
The development of microcephaly in children prenatally exposed to ZIKV is associated with low plasma levels of placentally transferred, pre-existing DENV IgG-NS1 antibodies. These data are compatible with a protective role of anti-NS1 IgG antibodies against ZIKV infection during pregnancy and highlight the promising role of NS1 as an orthoflavivirus vaccine target in high-risk populations.
妊娠期寨卡病毒（ZIKV）感染与先天性寨卡综合征（CZS）的发生有关，先天性寨卡综合征包括小头畸形和胎儿死亡。黄病毒属特异性体液免疫的强度和质量此前已与先天性寨卡综合征的发生相关联。然而，ZIKV NS1特异性体液免疫在产前暴露于ZIKV的母婴及先天性寨卡综合征中的作用仍不明确。此外，鉴于大多数高危人群生活在登革病毒（DENV）流行地区，既往存在的DENV NS1特异性体液免疫与先天性寨卡综合征之间的关联尚不清楚。
在此，我们研究了328名在孕期有ZIKV感染临床诊断且血清学阳性的母婴，这些母婴纳入了2015 - 2016年哥伦比亚ZIKV疫情期间的病例。我们还进行了临床评估和儿科神经学随访。评估了母婴体内针对ZIKV和DENV的循环NS1特异性IgM和IgG的相对水平，并分析了其与小头畸形发生的关联。
孕妇体内的DENV和ZIKV IgG - NS1抗体可经胎盘转移，这种转移及其在儿童体内的持续时间取决于母体抗体水平。我们报告称，较高浓度的既往存在的DENV而非ZIKV IgG - NS1抗体与先天性寨卡综合征相关小头畸形的风险降低有关。此外，我们观察到婴儿体内的IgM - NS1反应是长期的，且与不良结局的关联较小。
产前暴露于ZIKV的儿童发生小头畸形与胎盘转移的、既往存在的DENV IgG - NS1抗体的低血浆水平有关。这些数据与抗NS1 IgG抗体在孕期对ZIKV感染的保护作用相一致，并突出了NS1作为黄病毒属疫苗在高危人群中的潜在作用。
