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HIV 相关免疫激活会减弱孕妇接种 Tdap 免疫后针对 Tdap 的多效性 IgG 和记忆 B 细胞反应。

HIV-related immune activation attenuates polyfunctional IgG and memory B-cell responses to Tdap immunization during pregnancy.

机构信息

Institute for Medical Immunology and ULB Center for Research in Immunology (U-CRI), Faculty of Medicine, Université Libre de Bruxelles (ULB), Brussels, Belgium.

European Plotkin Institute for Vaccinology, Université Libre de Bruxelles (ULB), , Brussels, Belgium.

出版信息

EBioMedicine. 2024 Jun;104:105179. doi: 10.1016/j.ebiom.2024.105179. Epub 2024 Jun 7.

DOI:10.1016/j.ebiom.2024.105179
PMID:38848615
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11192781/
Abstract

BACKGROUND

Maternal pertussis vaccination with Tdap vaccine is recommended to protect newborns from severe postnatal infection. HIV-exposed uninfected (HEU) infants have a higher incidence of pertussis infection and may particularly benefit from maternal immunization. The impact of HIV infection on the quality of IgG and memory B cell (MBC) responses to Tdap vaccination in pregnant women (PW) living with HIV (PWH) is unknown.

METHODS

In this observational study, humoral immune responses to Tdap vaccination, including IgG levels, Fc-dependent effector functions, and MBC frequencies, were measured before and after vaccination in 40 PWH and 42 HIV-uninfected PW. Placental transfer of IgG and avidity were assessed in cord blood (CB). Soluble and cellular immune activation markers were quantified at baseline.

FINDINGS

One month after vaccination, PWH had lower frequencies of MBC compared with HIV-uninfected PW. At delivery, PWH had attenuated pertussis-specific IgG levels and Fc-dependent effector functions. Reduced levels of maternal vaccine polyfunctional IgG and IgG avidity were transferred to HEU as compared to HIV-unexposed newborns. After adjustment with ethnicity, maternal antibody levels and gestational age at vaccination, HIV infection was independently associated with decreased levels of PT specific-IgG in CB. Both maternal and neonatal pertussis-specific IgG responses as well as PT-specific IgG avidity were inversely correlated with maternal sCD14 levels before vaccination among PWH.

INTERPRETATION

Maternal HIV infection is associated with attenuated humoral immune responses to Tdap vaccination that correlate with sCD14. Suboptimal transfer of maternal immunity may further increase the risk of severe pertussis infection in HEU infants.

FUNDING

This work was supported by IRIS Fund managed by the Foundation Roi Baudouin [2017J1820690206902], Association Vésale pour la Recherche Médicale and the Medical Council of CHU Saint-Pierre and has been funded in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, US Department of Health and Human Services, under Award No. U19AI145825. N.D. is a clinical researcher and A.M. is Research Director at the Fonds de la Recherche Scientifique (F.R.S.-FNRS), Belgium. M.E.A. was partially supported by NIHNIAID1U19AI14825. This article is published with the support of the Fondation Universitaire of Belgium.

摘要

背景

Tdap 疫苗接种可预防母亲感染百日咳,从而保护新生儿免受严重的产后感染。艾滋病毒暴露但未感染的(HEU)婴儿百日咳感染率较高,可能特别受益于母亲免疫接种。HIV 感染对艾滋病毒感染者(PWH)孕妇接种 Tdap 疫苗后 IgG 和记忆 B 细胞(MBC)反应质量的影响尚不清楚。

方法

在这项观察性研究中,40 名 PWH 和 42 名 HIV 未感染者(PW)在接种 Tdap 疫苗前后测量了针对 Tdap 疫苗的体液免疫反应,包括 IgG 水平、Fc 依赖性效应功能和 MBC 频率。在脐血(CB)中评估 IgG 胎盘转移和亲和力。在基线时量化可溶性和细胞免疫激活标志物。

结果

接种后 1 个月,PWH 的 MBC 频率低于 HIV 未感染者。分娩时,PWH 的百日咳特异性 IgG 水平和 Fc 依赖性效应功能减弱。与未暴露于 HIV 的新生儿相比,向 HEU 转移的母体疫苗多效性 IgG 和 IgG 亲和力降低。在调整种族、母体抗体水平和接种疫苗时的胎龄后,HIV 感染与 CB 中 PT 特异性-IgG 水平降低独立相关。PWH 中,母体和新生儿百日咳特异性 IgG 反应以及 PT 特异性 IgG 亲和力与接种前母 CD14 水平呈负相关。

结论

母体 HIV 感染与 Tdap 疫苗接种的体液免疫反应减弱相关,这与 sCD14 相关。母体免疫的传递不足可能会进一步增加 HEU 婴儿严重百日咳感染的风险。

资金

本工作得到由 Roi Baudouin 基金会管理的 IRIS 基金[2017J1820690206902]、Vesale 协会和 Saint-Pierre 大学医疗中心医学委员会的支持,并得到美国国立卫生研究院过敏和传染病研究所、美国国立卫生研究院、美国卫生与公众服务部的部分资助,作为美国国立过敏和传染病研究所奖号 U19AI145825。N.D. 是一名临床研究员,A.M. 是比利时佛兰德斯研究基金会(F.R.S.-FNRS)的研究主任。M.E.A. 部分由 NIHNIAID1U19AI14825 资助。本文发表得到了比利时大学基金会的支持。

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