Several vaccines elicit lower efficacy or impaired immune responses in rural compared to urban settings, and in tropical low-income countries compared to high-income countries. An unresolved hypothesis is that immunomodulation by parasitic infections such as helminths (prevalent in rural tropical settings) contributes to suppression of vaccine responses. Among 1–17-year-old Ugandan residents of rural Schistosoma mansoni (Sm)-endemic islands and proximate urban communities with lower helminth exposure, we assessed plasma antibody and whole blood assay cytokine responses to tetanus toxoid (TT) and purified protein derivative of Mycobacterium tuberculosis (PPD). These were taken to represent recall responses to tetanus and BCG vaccination in infancy. PPD-specific responses are additionally induced by tuberculous and non-tuberculous mycobacterial exposure. Urban-rural comparisons showed that PPD-specific IFN-γ and IL-13 and TT-specific IL-13 and IgG concentrations were lower in the rural setting, but that PPD-specific IgE concentrations were higher. Among rural participants, Sm infection was inversely associated with PPD-specific IFN-γ, while nematode infection was positively associated with PPD-specific IgG. Among urban participants, Sm infection was positively associated with PPD-specific responses but inversely associated with TT-specific responses, while nematode infection was inversely associated with TT-specific IgG and IgG4, but no associations were observed with PPD-specific responses. Despite these associations, for the urban-rural comparisons there were no notable changes in test statistics after adjusting for current helminth infections, suggesting that helminths were not the sole explanation for the urban-rural differences observed. Helminths likely work in concert with other environmental exposures and operational factors to influence vaccine response.

与城市环境相比，在农村地区以及热带低收入国家与高收入国家相比，几种疫苗引起的功效降低或免疫反应受损。一个尚未解决的假设是，寄生虫感染（例如蠕虫）（在农村热带地区普遍存在）的免疫调节作用有助于抑制疫苗反应。在农村曼氏血吸虫病（Sm）流行岛和邻近城市的蠕虫接触率较低的1至17岁乌干达居民中，我们评估了血浆抗体和全血细胞因子对破伤风类毒素（TT）的反应以及纯化的蛋白衍生物结核分枝杆菌（PPD）。这些被认为代表婴儿期对破伤风和卡介苗接种的召回反应。结核性和非结核性分枝杆菌暴露也可引起PPD特异性反应。城乡比较表明，农村地区PPD特异性IFN-γ和IL-13和TT特异性IL-13和IgG浓度较低，而PPD特异性IgE浓度较高。在农村参与者中，Sm感染与PPD特异性IFN-γ呈负相关，而线虫感染与PPD特异性IgG呈正相关。在城市参与者中，Sm感染与PPD特异性应答呈正相关，而与TT特异性应答呈负相关，而线虫感染与TT特异性IgG和IgG4呈负相关，但未发现与PPD特异性应答相关。尽管存在这些关联，但在调整了当前的蠕虫感染后，对于城乡比较，测试统计数据没有显着变化，这表明，蠕虫并不是观察到的城乡差异的唯一解释。蠕虫可能会与其他环境暴露和操作因素协同工作，以影响疫苗反应。