Correlative outcomes of maternal immunization against RSV in cotton rats.

Correlative outcomes of maternal immunization against RSV in cotton rats.
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棉花大鼠母系RSV免疫的相关结果。

DOI:
10.1080/21645515.2022.2148499
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发表时间:
2022-12-30
影响因子:
4.8
通讯作者:
--
中科院分区:
医学3区
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--
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母体抗呼吸道合胞病毒(RSV)抗体可保护新生儿在生命的最初几周内免受RSV疾病的侵害。先前在棉鼠中进行的母体免疫的研究表明,在妊娠期间用与融合前F蛋白和野生型G蛋白组装的病毒样颗粒(VLP)对RSV致敏的母鼠进行单次免疫,提高了它们的RSV血清抗体浓度,并在生命早期保护幼崽免受RSV攻击。我们通过评价连续两次妊娠免疫母鼠的窝仔对RSV感染的反应来扩展这些发现。使用接种VLP和未接种疫苗的母鼠的RSV致敏群体,我们定义了母鼠和窝仔的RSV中和抗体(NA)之间的相关性;窝仔的NA和保护之间的相关性;窝仔的NA和它们的肺中选择的细胞因子的表达之间的相关性,第一次或第二次妊娠。还评价了肺部病理学。我们发现分娩时母鼠的NA滴度与其第一窝和第二窝的NA之间呈正相关,而窝NA与RSV攻击保护之间呈负相关。在出生后的不同时间,即使在没有可检测到的NA的情况下,接种母鼠也可调节第一窝和第二窝中IFNγ和IL-6的mRNA表达以及肺病理学。母体RSV疫苗接种增强了转移到后代的抗体水平及其对攻击的保护。重要的是,母体疫苗接种也影响了后代肺部的免疫和炎症反应,直到成熟,并且在母体转移的NA的抗病毒作用减弱或不再检测到之后。
Maternal anti-respiratory syncytial virus (RSV) antibodies protect neonates from RSV disease throughout first weeks of life. Previous studies of maternal immunization in cotton rats showed that a single immunization during pregnancy of RSV-primed dams with virus-like particles (VLPs) assembled with pre-fusion F protein and the wild type G protein boosted their RSV serum antibody concentration and protected pups early in life against RSV challenge. We extended these findings by evaluating responses to RSV infection in litters from two consecutive pregnancies of immunized dams. Using an RSV-primed population of VLP-vaccinated and unvaccinated dams, we defined correlations between dams’ and litters’ RSV neutralizing antibodies (NA); between litters’ NA and protection; and between litter’s NA and their lung expression of selected cytokines, of a first or of a second pregnancy. Lung pathology was also evaluated. We found positive correlation between the NA titers in the dams at delivery and the NA in their first and second litters and negative correlations between the litters’ NA and protection from RSV challenge. Vaccination of dams modulated the mRNA expression for IFNγ and IL-6 and lung pathology in the first and in the second litter at different times after birth, even in the absence of detectable NA. Maternal RSV vaccination enhanced the levels of antibodies transferred to offspring and their protection from challenge. Importantly, maternal vaccination also impacted the immunological and inflammatory response of the offspring’s lungs well into maturity, and after the antiviral effect of maternally transferred NA waned or was no longer detectable.
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发表时间: 2019-02-15
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