Clinical and Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Department of Systems Medicine and.
JCI Insight. 2024 Apr 11;9(10):e177182. doi: 10.1172/jci.insight.177182.
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.
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。