BCG Vaccination Enhances the Immunogenicity of Subsequent Influenza Vaccination in Healthy Volunteers: A Randomized, Placebo-Controlled Pilot Study
BCG Vaccination Enhances the Immunogenicity of Subsequent Influenza Vaccination in Healthy Volunteers: A Randomized, Placebo-Controlled Pilot Study
复制标题
DOI：
10.1093/infdis/jiv332
复制
发表时间：
2015-12-15
影响因子：
6.4
通讯作者：
Netea, Mihai G.
中科院分区：
文献类型：
--
作者：
Leentjens, Jenneke;Kox, Matthijs;Netea, Mihai G.
背景资料。与流感相关的发病率和死亡率仍然很高。季节性疫苗接种是流感管理的支柱，但并不总是产生保护性抗体效价。卡介苗接种与髓系抗原提呈细胞功能增强有关的非特异性效应已有报道。我们假设卡介苗接种也能增强对流感疫苗的免疫应答。健康志愿者随机接受卡介苗减毒活疫苗(n=20)或安慰剂(n=20)，14天后肌肉注射三价流感疫苗。检测血凝抑制(HI)抗体和体外白细胞反应检测细胞免疫功能。在接种卡介苗的受试者中，与安慰剂组相比，对2009年大流行甲型H1N1流感疫苗株的HI抗体反应显著增强，并有更快的血清转换的趋势。此外，接种卡介苗后，除了增强促炎症的白细胞反应外，还观察到流感疫苗的非特异性效应，并调节了对无关病原体的细胞因子反应。在接种流感疫苗之前接种卡介苗，结果是对2009年甲型H1N1大流行性流感疫苗株的功能性抗体反应的增加和加速。这些结果可能会对疫苗接种策略的设计产生影响，并可能导致疫苗接种效果的提高。
Background. Influenza-related morbidity and mortality remain high. Seasonal vaccination is the backbone of influenza management but does not always result in protective antibody titers. Nonspecific effects of BCG vaccination related to enhanced function of myeloid antigen-presenting cells have been reported. We hypothesized that BCG vaccination could also enhance immune responses to influenza vaccination.Methods. Healthy volunteers received either live attenuated BCG vaccine (n = 20) or placebo (n = 20) in a randomized fashion, followed by intramuscular injection of trivalent influenza vaccine 14 days later. Hemagglutination-inhibiting (HI) antibodies and cellular immunity measured by ex vivo leukocyte responses were assessed.Results. In BCG-vaccinated subjects, HI antibody responses against the 2009 pandemic influenza A(H1N1) vaccine strain were significantly enhanced, compared with the placebo group, and there was a trend toward more-rapid seroconversion. Additionally, apart from enhanced proinflammatory leukocyte responses following BCG vaccination, nonspecific effects of influenza vaccination were also observed, with modulation of cytokine responses against unrelated pathogens.Conclusions. BCG vaccination prior to influenza vaccination results in a more pronounced increase and accelerated induction of functional antibody responses against the 2009 pandemic influenza A(H1N1) vaccine strain. These results may have implications for the design of vaccination strategies and could lead to improvement of vaccination efficacy.