Influenza subtype-specific maternal antibodies protect offspring against infection but inhibit vaccine-induced immunity and protection in mice.
Influenza subtype-specific maternal antibodies protect offspring against infection but inhibit vaccine-induced immunity and protection in mice.
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DOI：
10.1016/j.vaccine.2022.10.003
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发表时间：
2022-11-08
期刊：
影响因子：
5.5
通讯作者：
Klein, Sabra L
中科院分区：
文献类型：
--
作者：
Creisher, Patrick S;Campbell, Ariana D;Perry, Jamie L;Roznik, Katerina;Burd, Irina;Klein, Sabra L
怀孕期间感染甲型流感病毒 (IAV) 或接种疫苗后，母源抗体会在子宫内和哺乳期间转移给后代。后代的年龄和性别可能对母体免疫力的转移和对后代的影响产生不同的影响。为了评估母体 IAV 感染对后代免疫力的影响，我们在胚胎第 10 天给怀孕小鼠鼻内接种了亚致死剂量的小鼠适应 (ma) H1N1、maH3N2 或培养基（模拟）。在感染 IAV 的母鼠的后代中，母体亚型特异性抗体在出生后第 23 天 (PND) 达到峰值，在 PND 50 期间仍然可检测到，并且 PND 无法检测到。男女均为 105。当后代在 PND 23 时接受同源 IAV 攻击时，与模拟接种母鼠的后代相比，雄性和雌性后代的肺部病毒清除率更高，发病率和死亡率更低。在 PND 23 时针对同源 IAV 的灭活流感疫苗 (IIV) 导致 IAV 后代受到活病毒攻击后疫苗诱导的抗体反应和保护作用低于模拟感染的母鼠，这种效应在雌性后代中比雄性后代中更为明显。在 PND 105 时，母体感染状态没有影响，但疫苗接种在 IAV 感染和模拟接种母鼠的雌性后代中诱导出更强的抗体反应和针对攻击的保护作用。为了确定母体抗体或感染是否干扰了生命早期疫苗诱导的免疫和保护，在 PND 23 或 105 时对后代进行了疫苗接种并针对异亚型 IAV（即与母体不同的 IAV 组）进行攻击。异亚型 IAV 母体免疫不会影响 IIV 后的抗体反应或任何年龄的接种疫苗的后代在活 IAV 攻击后的保护。因此，亚型特异性母体 IAV 抗体提供的保护与后代性别无关，但会干扰疫苗诱导的免疫和后代保护，对女性的影响比男性更明显。
Following influenza A virus (IAV) infection or vaccination during pregnancy, maternal antibodies are transferred to offspring in utero and during lactation. The age and sex of offspring may differentially impact the transfer and effects of maternal immunity on offspring. To evaluate the effects of maternal IAV infection on immunity in offspring, we intranasally inoculated pregnant mice with sublethal doses of mouse-adapted (ma) H1N1, maH3N2, or media (mock) at embryonic day 10. In offspring of IAV-infected dams, maternal subtype-specific antibodies peaked at postnatal day (PND) 23, remained detectable through PND 50, and were undetectable by PND 105 in both sexes. When offspring were challenged with homologous IAV at PND 23, both male and female offspring had greater clearance of pulmonary virus and less morbidity and mortality than offspring from mock-inoculated dams. Inactivated influenza vaccination (IIV) against homologous IAV at PND 23 caused lower vaccine-induced antibody responses and protection following live virus challenge in offspring from IAV than mock-infected dams, with this effect being more pronounced among female than male offspring. At PND 105, there was no impact of maternal infection status, but vaccination induced greater antibody responses and protection against challenge in female than male offspring of both IAV-infected and mock-inoculated dams. To determine if maternal antibody or infection interfered with vaccine-induced immunity and protection in early life, offspring were vaccinated and challenged against a heterosubtypic IAV (i.e., different IAV group than dam) at PND 23 or 105. Heterosubtypic IAV maternal immunity did not affect antibody responses after IIV or protection after live IAV challenge of vaccinated offspring at either age. Subtype-specific maternal IAV antibodies, therefore, provide protection independent of offspring sex but interfere with vaccine-induced immunity and protection in offspring with more pronounced effects among females than males.