B 细胞免疫和疫苗诱导的抗体保护表明，目前在非洲莫桑比克的围产期 HIV 感染婴儿中的疫苗接种计划无效。
B-cell immunity and vaccine induced antibody protection reveal the inefficacy of current vaccination schedule in infants with perinatal HIV-infection in Mozambique, Africa.
机构信息
Clinical Immunology and Vaccinology Unit, Bambino Gesù Children's Hospital, IRCCS, Rome 00165, Italy; Chair of Pediatrics, Department of Systems Medicine, University of Rome "Tor Vergata", Rome 00133, Italy.
Department of Microbiology and Immunology, Miami Center for AIDS Research, Miller School of Medicine, University of Miami, Miami, United States.
出版信息
EBioMedicine. 2023 Jul;93:104666. doi: 10.1016/j.ebiom.2023.104666. Epub 2023 Jul 3.
BACKGROUND
Despite antiretroviral treatment (ART), immune dysfunction persists in children with perinatal HIV infection (HEI). Here we investigated the impact of HIV status on maternal antibody (Ab) passage, long-term vaccine induced immunity and B-cell maturation.
METHODS
46 HIV Exposed Uninfected (HEU), 43 HEI, and 15 HIV unexposed uninfected (HUU) infants were vaccinated with 3 doses of DTaP-HepB-Hib-PCV10-OP at 2, 3, and 4 months at Matola Provincial Hospital, Maputo, Mozambique. Tetanus toxoid specific (TT) IgG, HIV Ab and B-cell phenotype characteristics were evaluated at entry, pre-ART, 5, 10, and 18 months in this longitudinal cohort study.
FINDINGS
Baseline (maternal) plasma TT Ab levels were significantly lower in HEI compared to both HEU and HUU and a faster decay of TT Ab was observed in HEI compared to HEU with significantly lower TT Ab levels at 10 and 18 months of age. TT unprotected (UP) (≤0.1 IU/mL) HEI showed higher HIV-RNA at entry and higher longitudinal HIV viremia (Area Under the Curve) compared to TT protected (P) HEI. A distinct HIV-Ab profile was found at entry in HEI compared to HEU. B-cell phenotype showed a B-cell perturbation in HEI vs HEU infants at entry (mean age 40.8 days) with lower transitional CD10+CD19+ B-cells and IgD+CD27- naive B-cells and an overall higher frequency of IgD-CD27- double negative B-cell subsets in HEI.
INTERPRETATION
B-cell perturbation, presenting with higher double negative IgD-CD27- B-cells was observed in neonatal age and may play a major role in the B-cell exhaustion in HEI. The ability to maintain TT protective Ab titers over time is impaired in HEI with uncontrolled viral replication and the current vaccination schedule is insufficient to provide long-term protection against tetanus.
FUNDING
This work was supported by: NIH grant to SP (5R01AI127347-05); Children's Hospital Bambino Gesú (Ricerca corrente 2019) to NC, and Associazione Volontari Bambino Gesù to PP.
背景
尽管接受了抗逆转录病毒治疗（ART），但围产期感染 HIV 的儿童（HEI）仍存在免疫功能障碍。在这里，我们研究了 HIV 状态对母体抗体（Ab）传递、长期疫苗诱导的免疫和 B 细胞成熟的影响。
方法
46 名 HIV 暴露未感染（HEU）、43 名 HEI 和 15 名 HIV 未暴露未感染（HUU）婴儿在马托拉省医院（莫桑比克马普托）于 2、3 和 4 个月龄时接受了 3 剂 DTaP-HepB-Hib-PCV10-OP 疫苗接种。在这项纵向队列研究中，在进入研究、ART 前、5、10 和 18 个月时，评估破伤风类毒素特异性（TT）IgG、HIV Ab 和 B 细胞表型特征。
结果
与 HEU 和 HUU 相比，HEI 的基线（母体）血浆 TT Ab 水平显著降低，与 HEU 相比，HEI 中 TT Ab 的衰减速度更快，在 10 和 18 个月龄时 TT Ab 水平显著降低。TT 未保护（UP）（≤0.1 IU/mL）的 HEI 在进入研究时 HIV-RNA 更高，纵向 HIV 病毒血症（曲线下面积）更高，与 TT 保护（P）的 HEI 相比。与 HEU 相比，HEI 在进入研究时存在明显不同的 HIV-Ab 特征。在进入研究时，HEI 的 B 细胞表型与 HEU 婴儿相比存在 B 细胞紊乱，表现为幼稚的 CD10+CD19+B 细胞和 IgD+CD27-的过渡性 B 细胞以及 IgD-CD27-双阴性 B 细胞亚群的总体频率更高。
解释
在新生儿时期观察到 B 细胞紊乱，表现为更高的 IgD-CD27-双阴性 B 细胞，可能在 HEI 的 B 细胞耗竭中起主要作用。HEI 中无法控制的病毒复制会损害 TT 保护性 Ab 滴度随时间的维持能力，而当前的疫苗接种计划不足以提供针对破伤风的长期保护。
资金
这项工作得到了 NIH 资助（SP，5R01AI127347-05）；Bambino Gesù 儿童医院（Ricerca corrente 2019）资助 NC；以及 Volontari Bambino Gesù 协会资助 PP。
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