Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
J Immunol. 2011 Jun 1;186(11):6173-81. doi: 10.4049/jimmunol.1100264. Epub 2011 Apr 29.
Mechanisms underlying failure of novel 2009 H1N1 influenza vaccine-induced Ab responses in HIV-infected persons are poorly understood. This study prospectively evaluated 16 HIV-infected patients on combination antiretroviral therapy and eight healthy controls (HC) who received a single 15 μg dose of nonadjuvanted novel 2009 H1N1 influenza vaccine during the 2009 H1N1 epidemic. Peripheral blood was collected at baseline (T0) and at 7 d (T1) and 28 d (T2) postvaccination for evaluation of immune responses. Prevaccination hemagglutination inhibition Ab titer was <1:20 in all except one study participant. At T2, all HC and 8 out of 16 patients (50%) developed a vaccine-induced Ab titer of ≥ 1:40. Vaccine responder (R) and vaccine nonresponder patients were comparable at T0 in age, CD4 counts, virus load, and B cell immunophenotypic characteristics. At T2, HC and R patients developed an expansion of phenotypic and functional memory B cells and ex vivo H1N1-stimulated IgG Ab-secreting cells in an ELISPOT assay. The memory B cell response was preceded by a significant expansion of plasmablasts and spontaneous H1N1-specific Ab-secreting cells at T1. At T2, HC and R patients also exhibited significant increases in serum IL-21 levels and in the frequency and mean fluorescence intensity of IL-21R-expressing B cells, which correlated with serum H1N1 Ab titers. Vaccine nonresponder patients failed to develop the above-described vaccine-induced immunologic responses. The novel association of novel 2009 H1N1 vaccine-induced Ab responses with IL-21/IL-21R upregulation and with development of memory B cells and plasmablasts has implications for future research in vaccine design.
新型 2009 年 H1N1 流感疫苗诱导的抗体反应在 HIV 感染者中失败的机制尚不清楚。本研究前瞻性评估了 16 名接受联合抗逆转录病毒治疗的 HIV 感染者和 8 名健康对照者（HC），他们在 2009 年 H1N1 流感大流行期间接受了单次 15μg 剂量的非佐剂新型 2009 年 H1N1 流感疫苗。在接种疫苗前（T0）和接种后 7 天（T1）和 28 天（T2）采集外周血，评估免疫反应。除一名研究参与者外，所有研究参与者的血凝抑制抗体滴度均<1:20。在 T2 时，所有 HC 和 16 名患者中的 8 名（50%）产生了≥1:40 的疫苗诱导抗体滴度。在 T0 时，疫苗应答者（R）和疫苗无应答者在年龄、CD4 计数、病毒载量和 B 细胞免疫表型特征方面无差异。在 T2 时，HC 和 R 患者在 ELISPOT 测定中均发展出表型和功能记忆 B 细胞和体外 H1N1 刺激的 IgG 抗体分泌细胞的扩增。在 T1 时，记忆 B 细胞反应之前，浆母细胞和自发性 H1N1 特异性抗体分泌细胞显著扩增。在 T2 时，HC 和 R 患者还表现出血清 IL-21 水平以及表达 IL-21R 的 B 细胞的频率和平均荧光强度显著增加，与血清 H1N1 抗体滴度相关。疫苗无应答者未能产生上述疫苗诱导的免疫反应。新型 2009 年 H1N1 疫苗诱导的抗体反应与 IL-21/IL-21R 的上调以及记忆 B 细胞和浆母细胞的发育之间的新关联，对未来疫苗设计的研究具有重要意义。
