Murine Model of Maternal Immunization Demonstrates Protective Role for Antibodies That Mediate Antibody-Dependent Cellular Cytotoxicity in Protecting Neonates From Herpes Simplex Virus Type 1 and Type 2
Murine Model of Maternal Immunization Demonstrates Protective Role for Antibodies That Mediate Antibody-Dependent Cellular Cytotoxicity in Protecting Neonates From Herpes Simplex Virus Type 1 and Type 2
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DOI：
10.1093/infdis/jiz521
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发表时间：
2020-03-01
影响因子：
6.4
通讯作者：
Herold, Betsy C.
中科院分区：
文献类型：
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作者：
Kao, Carol M.;Goymer, Jessica;Herold, Betsy C.
背景。新生儿单纯疱疹病毒（HSV）疾病导致不可接受的发病率和死亡率。对自然感染的主要体液免疫反应是中和抗体（Abs）。然而，激活Fc γ受体（Fc γ Rs）并介导抗体依赖性细胞介导的细胞毒性（ADCC）的抗体可能在保护中发挥主导作用。在成年小鼠中，一种缺失糖蛋白- d （Delta gD-2）的单周期HSV候选疫苗可诱导ADCC，对HSV疾病提供完全保护，并防止潜伏期的建立。被动转移研究表明，抗体具有足够的保护作用。本研究验证了母体接种Delta gD-2对新生儿有保护作用的假设。C57BL/6雌性小鼠每隔3周接种Delta gD-2疫苗，幼鼠在出生后不同时间接种致死剂量的HSV-1或HSV-2。测定抗体和免疫细胞的浓度和功能。在感染HSV-1或HSV-2致死性攻击后，母体δ gD-2免疫提供了显著的保护并减少了病毒传播。保护作用与经胎盘或母乳获得的抗体介导ADCC相关。当幼鼠在出生第1天受到挑战时，保护作用降低，这与新生细胞介导抗体依赖性细胞杀伤的能力下降有关。介导ADCC的抗体对新生儿HSV具有显著的保护作用。
Background. Neonatal herpes simplex virus (HSV) disease results in unacceptable morbidity and mortality. The primary humoral immune response to natural infection is neutralizing antibodies (Abs). However, Abs that activate Fc gama receptors (Fc gamma Rs) and mediate antibody-dependent cell-mediated cytotoxicity (ADCC) may play a dominant role in protection. In adult mice, a single-cycle HSV candidate vaccine deleted in glycoprotein-D (Delta gD-2) that induces ADCC provided complete protection against HSV disease and prevented the establishment of latency. Passive transfer studies showed that Abs were sufficient for protection. The current study tested the hypothesis that maternal immunization with Delta gD-2 would protect neonates.Methods. C57BL/6 female mice were vaccinated 3 weeks apart with Delta gD-2, and pups were challenged at different times postnatally with lethal doses of HSV-1 or HSV-2. Concentration and functionality of Abs and immune cells were assessed.Results. Maternal Delta gD-2 immunization provided significant protection and reduced viral dissemination after lethal challenge with HSV-1 or HSV-2. Protection correlated with Abs acquired transplacentally or from breastmilk that mediated ADCC. Protection was reduced when pups were challenged on Day 1 of life, and this was associated with decreased ability of newborn cells to mediate Ab-dependent cell killing.Conclusions. Antibodies mediating ADCC provide significant protection against neonatal HSV.