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病毒体佐剂三价流感疫苗在异基因干细胞移植受者中的免疫原性。

Immunogenicity of virosomal adjuvanted trivalent influenza vaccination in allogeneic stem cell transplant recipients.

作者信息

Ambati A, Einarsdottir S, Magalhaes I, Poiret T, Bodenstein R, LeBlanc K, Brune M, Maeurer M, Ljungman P

机构信息

Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden.

Department of Medicine, Karolinska Institutet, Huddinge, Sweden.

出版信息

Transpl Infect Dis. 2015 Jun;17(3):371-9. doi: 10.1111/tid.12382. Epub 2015 Jun 1.

Abstract

BACKGROUND

Influenza vaccination is generally recommended to hematopoietic stem cell transplant (HSCT) recipients. However, the seasonal subunit vaccination response is frequently suboptimal, and alternate more efficient vaccination systems must be examined. We compared the immunogenicity of an adjuvanted virosomal influenza and subunit vaccine in HSCT recipients.

METHODS

The immunogenicity after a single dose (0.5 mL) of adjuvanted trivalent virosomal vaccination was evaluated in a study cohort of 21 HSCT recipients and compared to a control cohort of 30 HSCT recipients who received a single dose (0.5 mL) of non-adjuvanted seasonal trivalent subunit vaccination over 4 seasons from 2010 to 2014. Whole blood interferon-gamma (IFN-γ) release assays were tested, both before and 30 days after vaccination, in response to influenza pandemic (pdm) H1N1, H3N2, and B antigens. HLA-A*02 dextramers, to gauge for the absolute number of antigen-specific CD8(+) T-cells, and pdm 2009 hemagglutinin inhibition (HI) assays, to test for neutralizing antibodies, were used as immunological readouts.

RESULTS

The pdm HI titers were poor in both cohorts with only 23% (5/21) after virosomal vaccination and 13.3% (4/30) in the seasonal vaccine cohort having protective titers (≥40). The delta change of IFN-γ production in response to influenza pdm H1N1 (P = 0.005) and influenza B antigens (P = 0.01) were significantly elevated in blood from individuals who received the virosomal as compared to the seasonal vaccine. The IFN-γ response to pdm H1N1 was stronger (P < 0.001), as compared to seasonal vaccination, in patients vaccinated >6 month post HSCT. We detected a significant increase in the frequency of matrix 1 (GILGFVTL) dextramer-specific CD8(+) T-cells after the virosomal vaccine (P = 0.01). No differences were seen in the hemagglutinin-specific CD8(+) T-cells between the 2 cohorts.

CONCLUSION

Vaccination using a virosomal delivery system is beneficial in eliciting robust cellular immune responses to pdm H1N1 influenza in SCT recipients.

摘要

背景

一般建议造血干细胞移植(HSCT)受者接种流感疫苗。然而,季节性亚单位疫苗接种反应常常不理想,必须研究其他更有效的疫苗接种系统。我们比较了佐剂化病毒体流感疫苗和亚单位疫苗在HSCT受者中的免疫原性。

方法

在21名HSCT受者的研究队列中评估单剂量(0.5 mL)佐剂化三价病毒体疫苗接种后的免疫原性,并与2010年至2014年4个季节中接受单剂量(0.5 mL)非佐剂化季节性三价亚单位疫苗接种的30名HSCT受者的对照队列进行比较。在接种疫苗前和接种后30天,针对甲型H1N1流感大流行(pdm)、H3N2和B型抗原进行全血干扰素-γ(IFN-γ)释放试验。使用HLA-A*02右旋糖酐聚合物来测定抗原特异性CD8(+) T细胞的绝对数量,使用2009年甲型H1N1流感血凝素抑制(HI)试验来检测中和抗体,作为免疫学读数。

结果

两个队列中的pdm HI滴度均较低,病毒体疫苗接种后只有23%(5/21),季节性疫苗队列中有13.3%(4/30)具有保护性滴度(≥40)。与季节性疫苗相比,接受病毒体疫苗的个体血液中,针对甲型H1N1流感大流行(P = 0.005)和B型流感抗原(P = 0.01)的IFN-γ产生的变化显著升高。与季节性疫苗接种相比,HSCT后>6个月接种疫苗的患者对pdm H1N1的IFN-γ反应更强(P < 0.001)。我们检测到病毒体疫苗接种后基质1(GILGFVTL)右旋糖酐聚合物特异性CD8(+) T细胞的频率显著增加(P = 0.01)。两个队列之间的血凝素特异性CD8(+) T细胞未见差异。

结论

使用病毒体递送系统进行疫苗接种有利于在SCT受者中引发对pdm H1N1流感的强大细胞免疫反应。

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