Division of Infectious Diseases and HIV Medicine, Department of Medicine, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of America.
PATRU, School of Medicine, Emory University, Atlanta, Georgia, United States of America.
PLoS Negl Trop Dis. 2023 Jul 5;17(7):e0011089. doi: 10.1371/journal.pntd.0011089. eCollection 2023 Jul.
Schistosomiasis is a disease caused by parasitic flatworms of the Schistosoma spp., and is increasingly recognized to alter the immune system, and the potential to respond to vaccines. The impact of endemic infections on protective immunity is critical to inform vaccination strategies globally. We assessed the influence of Schistosoma mansoni worm burden on multiple host vaccine-related immune parameters in a Ugandan fishing cohort (n = 75) given three doses of a Hepatitis B (HepB) vaccine at baseline and multiple timepoints post-vaccination. We observed distinct differences in immune responses in instances of higher worm burden, compared to low worm burden or non-infected. Concentrations of pre-vaccination serum schistosome-specific circulating anodic antigen (CAA), linked to worm burden, showed a significant bimodal distribution associated with HepB titers, which was lower in individuals with higher CAA values at month 7 post-vaccination (M7). Comparative chemokine/cytokine responses revealed significant upregulation of CCL19, CXCL9 and CCL17 known to be involved in T cell activation and recruitment, in higher CAA individuals, and CCL17 correlated negatively with HepB titers at month 12 post-vaccination. We show that HepB-specific CD4+ T cell memory responses correlated positively with HepB titers at M7. We further established that those participants with high CAA had significantly lower frequencies of circulating T follicular helper (cTfh) subpopulations pre- and post-vaccination, but higher regulatory T cells (Tregs) post-vaccination, suggesting changes in the immune microenvironment in high CAA could favor Treg recruitment and activation. Additionally, we found that changes in the levels of innate-related cytokines/chemokines CXCL10, IL-1β, and CCL26, involved in driving T helper responses, were associated with increasing CAA concentration. This study provides further insight on pre-vaccination host responses to Schistosoma worm burden which will support our understanding of vaccine responses altered by pathogenic host immune mechanisms and memory function and explain abrogated vaccine responses in communities with endemic infections.
血吸虫病是一种由血吸虫属寄生虫引起的疾病，人们越来越认识到它会改变免疫系统，并有可能对疫苗产生反应。地方性感染对保护性免疫的影响对于在全球范围内告知疫苗接种策略至关重要。我们评估了乌干达渔业队列（n = 75）中曼氏血吸虫虫负荷对多种宿主疫苗相关免疫参数的影响，该队列在基线和接种疫苗后多个时间点接受了三剂乙型肝炎（HepB）疫苗。我们观察到，在高虫负荷情况下，与低虫负荷或未感染相比，免疫反应存在明显差异。与虫负荷相关的接种前血清血吸虫特异性循环阳极抗原（CAA）浓度表现出与 HepB 滴度显著的双峰分布相关，在接种后 7 个月（M7）时 CAA 值较高的个体中，HepB 滴度较低。比较趋化因子/细胞因子反应表明，在 CAA 较高的个体中，CCL19、CXCL9 和 CCL17 的显著上调与 T 细胞激活和募集有关，并且 CCL17 在接种后 12 个月（M12）时与 HepB 滴度呈负相关。我们表明，HepB 特异性 CD4+T 细胞记忆反应与 M7 时的 HepB 滴度呈正相关。我们进一步证实，高 CAA 组的参与者在接种前后循环滤泡辅助 T 细胞（cTfh）亚群的频率明显降低，但接种后 Treg 细胞升高，这表明高 CAA 中免疫微环境的变化可能有利于 Treg 的募集和激活。此外，我们发现，参与驱动 T 辅助反应的固有相关细胞因子/趋化因子 CXCL10、IL-1β 和 CCL26 的水平变化与 CAA 浓度的增加有关。这项研究进一步了解了宿主对血吸虫虫负荷的接种前反应，这将支持我们对疫苗反应的理解，疫苗反应被致病性宿主免疫机制和记忆功能改变，解释了在地方性感染社区中疫苗反应的减弱。
