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用佐剂重组受体结合域蛋白进行母体免疫可在幼猴中提供针对严重急性呼吸综合征冠状病毒2的免疫保护。

Maternal Immunization with Adjuvanted Recombinant Receptor-Binding Domain Protein Provides Immune Protection against SARS-CoV-2 in Infant Monkeys.

作者信息

Coe Christopher L, Nimityongskul Francesca, Lubach Gabriele R, Luke Kimberly, Rancour David, Schomburg Fritz M

机构信息

Harlow Center for Biological Psychology, University of Wisconsin-Madison, Madison, WI 53715, USA.

Boost Biopharma, Madison, WI 53713, USA.

出版信息

Vaccines (Basel). 2024 Aug 20;12(8):929. doi: 10.3390/vaccines12080929.

Abstract

Maternal vaccinations administered prior to conception or during pregnancy enhance the immune protection of newborn infants against many pathogens. A feasibility experiment was conducted to determine if monkeys can be used to model the placental transfer of maternal antibody against SARS-CoV-2. Six adult rhesus monkeys were immunized with adjuvanted recombinant-protein antigens comprised of receptor-binding domain human IgG1-Fc fusion proteins (RBD-Fc) containing protein sequences from the ancestral-Wuhan or Gamma variants. The female monkeys mounted robust and sustained anti-SARS-CoV-2 antibody responses. Blood samples collected from their infants after delivery verified prenatal transfer of high levels of spike-specific IgG, which were positively correlated with maternal IgG titers at term. In addition, an in vitro test of ACE2 neutralization indicated that the infants' IgG demonstrated antigen specificity, reflecting prior maternal immunization with either Wuhan or Gamma-variant antigens. All sera showed stronger ACE2-RBD binding inhibition when variants in the assay more closely resembled the vaccine RBD sequence than with more distantly related variants (i.e., Delta and Omicron). Monkeys are a valuable animal model for evaluating new vaccines that can promote maternal and infant health. Further, the findings highlight the enduring nature and safety of the immune protection elicited by an adjuvanted recombinant RBD-Fc vaccine.

摘要

在受孕前或怀孕期间进行的母体疫苗接种可增强新生儿对多种病原体的免疫保护。进行了一项可行性实验,以确定猴子是否可用于模拟母体抗SARS-CoV-2抗体的胎盘转移。六只成年恒河猴用由受体结合域人IgG1-Fc融合蛋白(RBD-Fc)组成的佐剂重组蛋白抗原进行免疫,该融合蛋白包含来自原始武汉株或伽马变异株的蛋白序列。雌性猴子产生了强烈且持续的抗SARS-CoV-2抗体反应。分娩后从它们的婴儿采集的血样证实了高水平刺突特异性IgG的产前转移,这与足月时母体IgG滴度呈正相关。此外,一项ACE2中和体外试验表明,婴儿的IgG表现出抗原特异性,反映了母体先前用武汉株或伽马变异株抗原进行的免疫接种。当检测中的变异株与疫苗RBD序列更相似时,所有血清显示出比与关系更远的变异株(即德尔塔和奥密克戎)更强的ACE2-RBD结合抑制作用。猴子是评估可促进母婴健康的新疫苗的有价值动物模型。此外,这些发现突出了佐剂重组RBD-Fc疫苗引发的免疫保护的持久性和安全性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f9e/11359192/4b611fc4234b/vaccines-12-00929-g001.jpg

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