Immunomodulation and Vaccines Focus Area, Vaccine Research Theme, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine (MRC/UVRI and LSHTM) Uganda Research Unit, Entebbe, Uganda.
Medical Research Council (MRC) International Statistics and Epidemiology Group, Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Front Immunol. 2024 Aug 29;15:1460183. doi: 10.3389/fimmu.2024.1460183. eCollection 2024.
Variations in vaccine responses have been observed between populations. A role for helminth infections has been proposed due to their immunomodulatory properties. In a secondary analysis of data from a randomised trial assessing effects of anthelminthic treatment on vaccine responses, we examined associations between helminth infections at baseline prior to vaccine administration, and vaccine responses among adolescents (9-17 years) in Koome Islands, Lake Victoria, Uganda.
Participants received BCG [week 0], yellow fever (YF-17D), oral typhoid (Ty21a), HPV-prime [week 4], and HPV-boost, tetanus/diphtheria [week 28]. Outcomes were BCG-specific interferon-γ ELISpot responses and antibody responses to yellow-fever-, typhoid-, HPV-, tetanus- and diphtheria-specific antigens measured at two time points post vaccination. infection was determined as positive if either the plasma Circulating Anodic Antigen (CAA) assay or stool PCR were positive. Hookworm and were determined by stool PCR. Linear mixed effects regression was used to assess associations.
Among 478 adolescents, 70% were (Sm) infected and 23% hookworm infected at baseline. was associated with lower Typhi O:LPS-specific IgG responses (adjusted geometric mean ratio (aGMR) 0.69 (0.57-0.83)), and hookworm with higher diphtheria-specific IgG (aGMR 1.16 (1.02, 1.31)) and lower HPV-16-specific IgG (aGMR 0.70 (0.55, 0.90)) post-vaccination. High intensity was associated with lower BCG-specific interferon-γ and Typhi O:LPS-specific IgG.
We found inverse associations between and responses to two live vaccines, whereas hookworm was positively associated with diphtheria-specific IgG. These findings support the hypothesis that helminth infections can modulate vaccine responses, while also highlighting potential heterogeneity in the direction of these effects.
疫苗反应在不同人群中存在差异。由于寄生虫感染具有免疫调节特性，因此有人提出了寄生虫感染的作用。在评估驱虫治疗对疫苗反应影响的随机试验数据的二次分析中，我们检查了在乌干达维多利亚湖 Koome 岛接种疫苗前基线时寄生虫感染与青少年（9-17 岁）疫苗反应之间的关联。
参与者接受了卡介苗[第 0 周]、黄热病（YF-17D）、口服伤寒（Ty21a）、HPV-初免[第 4 周]和 HPV-加强、破伤风类毒素/白喉[第 28 周]。疫苗接种后两个时间点测量 BCG 特异性干扰素-γ ELISpot 反应以及对黄热病、伤寒、HPV、破伤风和白喉特异性抗原的抗体反应。如果血浆循环阳极抗原（CAA）检测或粪便 PCR 阳性，则认为存在感染。钩虫和旋毛虫通过粪便 PCR 确定。使用线性混合效应回归评估关联。
在 478 名青少年中，70%感染了 （Sm），23%感染了钩虫。在调整后的几何平均比（aGMR）为 0.69（0.57-0.83）后，感染与较低的伤寒 O：LPS 特异性 IgG 反应相关，而钩虫与较高的白喉特异性 IgG（aGMR 1.16（1.02，1.31））和较低的 HPV-16 特异性 IgG（aGMR 0.70（0.55，0.90））相关。高感染强度与较低的 BCG 特异性干扰素-γ和伤寒 O：LPS 特异性 IgG 相关。
我们发现 与两种活疫苗的反应之间存在负相关，而钩虫与白喉特异性 IgG 呈正相关。这些发现支持寄生虫感染可以调节疫苗反应的假设，同时也突出了这些影响的方向存在潜在的异质性。
