Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, 6526, GA, Nijmegen, The Netherlands.
Research Center for Vitamins and Vaccines, Bandim Health Project, Statens Serum Institut, DK-2300, Copenhagen, Denmark.
Eur J Clin Microbiol Infect Dis. 2020 Jun;39(6):1177-1184. doi: 10.1007/s10096-020-03813-y. Epub 2020 Feb 17.
The Vi polysaccharide typhoid fever vaccine (TFV) provides incomplete protection against typhoid fever. BCG, the vaccine against tuberculosis, can potentiate immune responses to other vaccines through induction of trained innate immunity and heterologous adaptive immunity. We performed an explorative, randomized, noncontrolled open trial to investigate whether BCG vaccination increases humoral and cellular response to TFV and whether BCG and TFV modulate nonspecific immune responses. Thirty volunteers were randomized to receive either TFV alone or BCG followed by TFV after 2 weeks. Ex vivo leukocyte responses and anti-Vi IgG antibody titers were measured 2 weeks and 3 months after TFV. BCG administration prior to TFV vaccination did not increase specific humoral or cellular immune responses to Salmonella typhi. TFV vaccination decreased pro-inflammatory responses to non-related stimuli. This effect was counteracted by prior BCG administration, which also led to decreased IL-10 and increased IL-22 responses to non-related stimuli. In an in vitro model of trained immunity TFV led to immunotolerance, which was partially reversed by BCG-induced trained immunity. BCG does not modulate adaptive immune responses to TFV but partially prevents inhibition of innate immune responses induced by TFV. Nonspecific effects of vaccines to unrelated microbial stimuli must be considered in the evaluation of their biological effects (ClinicalTrials.gov NCT02175420).
Vi 多糖伤寒疫苗（TFV）对伤寒的保护作用不完全。卡介苗（BCG）是预防结核病的疫苗，通过诱导训练有素的先天免疫和异源适应性免疫，能够增强对其他疫苗的免疫反应。我们进行了一项探索性、随机、非对照的开放性试验，以研究卡介苗接种是否会增加对 TFV 的体液和细胞反应，以及卡介苗和 TFV 是否会调节非特异性免疫反应。30 名志愿者被随机分为单独接种 TFV 组或接种 BCG 后 2 周再接种 TFV 组。在接种 TFV 后 2 周和 3 个月，测量了体外白细胞反应和抗 Vi IgG 抗体滴度。BCG 接种在前，TFV 接种在后，并未增加对伤寒沙门氏菌的特异性体液或细胞免疫反应。TFV 接种降低了对非相关刺激的促炎反应。BCG 接种前预先接种卡介苗可抵消这种作用，同时还导致对非相关刺激的 IL-10 减少和 IL-22 增加。在训练免疫的体外模型中，TFV 导致免疫耐受，而 BCG 诱导的训练免疫部分逆转了这种作用。BCG 不调节对 TFV 的适应性免疫反应，但部分防止了 TFV 诱导的先天免疫反应的抑制。在评估疫苗的生物学效应时，必须考虑到对无关微生物刺激的非特异性效应（ClinicalTrials.gov NCT02175420）。
