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围生期感染 HIV 的儿童对 4CMenB 疫苗表现出不同的免疫反应。

Children with perinatally acquired HIV exhibit distinct immune responses to 4CMenB vaccine.

机构信息

Clinical and Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

Department of Systems Medicine and.

出版信息

JCI Insight. 2024 Apr 11;9(10):e177182. doi: 10.1172/jci.insight.177182.

Abstract

Children with perinatally acquired HIV (PHIV) have special vaccination needs, as they make suboptimal immune responses. Here, we evaluated safety and immunogenicity of 2 doses of 4-component group B meningococcal vaccine in antiretroviral therapy-treated children with PHIV and healthy controls (HCs). Assessments included the standard human serum bactericidal antibody (hSBA) assay and measurement of IgG titers against capsular group B Neisseria meningitidis antigens (fHbp, NHBA, NadA). The B cell compartment and vaccine-induced antigen-specific (fHbp+) B cells were investigated by flow cytometry, and gene expression was investigated by multiplexed real-time PCR. A good safety and immunogenicity profile was shown in both groups; however, PHIV demonstrated a reduced immunogenicity compared with HCs. Additionally, PHIV showed a reduced frequency of fHbp+ and an altered B cell subset distribution, with higher fHbp+ frequency in activated memory and tissue-like memory B cells. Gene expression analyses on these cells revealed distinct mechanisms between PHIV and HC seroconverters. Overall, these data suggest that PHIV presents a diverse immune signature following vaccination. The impact of such perturbation on long-term maintenance of vaccine-induced immunity should be further evaluated in vulnerable populations, such as people with PHIV.

摘要

患有围生期获得性 HIV(PHIV)的儿童的免疫反应不佳,因此有特殊的疫苗接种需求。在这里,我们评估了接受抗逆转录病毒治疗的 PHIV 儿童和健康对照(HC)接受两剂 4 组分 B 群脑膜炎球菌疫苗的安全性和免疫原性。评估包括标准人类血清杀菌抗体(hSBA)测定和针对荚膜 B 群脑膜炎奈瑟菌抗原(fHbp、NHBA、NadA)的 IgG 滴度测量。通过流式细胞术研究 B 细胞区室和疫苗诱导的抗原特异性(fHbp+)B 细胞,并通过多重实时 PCR 研究基因表达。两组均显示出良好的安全性和免疫原性;然而,与 HC 相比,PHIV 表现出较低的免疫原性。此外,PHIV 显示出 fHbp+的频率降低和 B 细胞亚群分布的改变,激活的记忆和组织样记忆 B 细胞中的 fHbp+频率更高。对这些细胞的基因表达分析揭示了 PHIV 和 HC 血清转化者之间的不同机制。总的来说,这些数据表明 PHIV 在接种疫苗后呈现出多样化的免疫特征。这种干扰对易受影响人群(如 PHIV 患者)中疫苗诱导免疫的长期维持的影响应进一步评估。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbb0/11141905/5dac881a84f8/jciinsight-9-177182-g085.jpg

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