Division of Child Health, Menzies School of Health Research, Charles Darwin University, NT, Australia.
Division of Child Health, Menzies School of Health Research, Charles Darwin University, NT, Australia; Queensland Lung Transplant Service, The Prince Charles Hospital, QLD, Australia; School of Medicine, The University of Queensland, QLD, Australia.
Vaccine. 2015 Jan 3;33(2):321-6. doi: 10.1016/j.vaccine.2014.11.024. Epub 2014 Nov 22.
Endobronchial infections related to non-typeable Haemophilus influenzae (NTHi) are common in children and adults with suppurative airway disease such as bronchiectasis and COPD. Impaired cell mediated immune responses to NTHi have been described in these patients. Currently there are no interventions known to correct the deficiency in cell mediated immune responses to NTHi. The aim of this study was to determine if receipt of a conjugate vaccine containing protein D from H. influenzae is associated with improvement in NTHi-specific cytokine responses in children with chronic suppurative lung disease.
Blood mononuclear cells from 107 young children with chronic suppurative lung disease and 32 healthy control children were stimulated in vitro with NTHi. We compared the cytokine production of stimulated mononuclear cells from children who had received the pneumococcal H. influenzae protein D conjugate vaccine with cells from children who received pneumococcal vaccines without protein D. Protein D-specific IgG1 was quantified in plasma.
Children with chronic suppurative lung disease who received ≥ 3 doses of the protein D conjugate vaccine produced significantly more IFNγ than children who received the alternative vaccines without protein D (median 939 versus 338 pg/ml; p = 0.007). Importantly, the amount of IFNγ produced by those vaccinated with the conjugate vaccine approached the levels observed in cells from healthy children. The conjugate vaccine was also associated with small but significant increases in IL-13 (p < 0.001) and IL-5 (p = 0.007). Protein D-specific IgG1 levels correlated with the number of PHiD-CV doses (p = 0.02).
Vaccination with PHiD-CV is associated with improvements in NTHi-specific cell-mediated and humoral immune responses in children with chronic suppurative lung disease.
非典型流感嗜血杆菌(NTHi)引起的支气管内感染在支气管扩张症和 COPD 等化脓性气道疾病的儿童和成人中很常见。这些患者存在针对 NTHi 的细胞介导免疫应答受损。目前,尚无已知的干预措施可纠正针对 NTHi 的细胞介导免疫应答缺陷。本研究旨在确定是否接受含有流感嗜血杆菌蛋白 D 的结合疫苗与慢性化脓性肺病儿童的 NTHi 特异性细胞因子反应改善相关。
107 名患有慢性化脓性肺病的幼儿和 32 名健康对照儿童的血液单核细胞在体外用 NTHi 刺激。我们比较了接受肺炎球菌流感嗜血杆菌蛋白 D 结合疫苗的儿童刺激单核细胞产生的细胞因子与接受不含蛋白 D 的肺炎球菌疫苗的儿童的细胞因子。在血浆中定量测定蛋白 D 特异性 IgG1。
接受≥3 剂蛋白 D 结合疫苗的慢性化脓性肺病儿童产生的 IFNγ明显多于接受不含蛋白 D 的替代疫苗的儿童(中位数 939 与 338 pg/ml;p = 0.007)。重要的是,用结合疫苗接种的儿童产生的 IFNγ接近健康儿童细胞中观察到的水平。该结合疫苗还与 IL-13(p < 0.001)和 IL-5(p = 0.007)的小但显著增加相关。蛋白 D 特异性 IgG1 水平与 PHiD-CV 剂量呈正相关(p = 0.02)。
接种 PHiD-CV 与慢性化脓性肺病儿童 NTHi 特异性细胞介导和体液免疫反应的改善相关。