Genetics, Vaccines and Pediatric Infectious Diseases Research Group (GENVIP), Instituto de Investigación Sanitaria de Santiago (IDIS) and Universidad de Santiago de Compostela (USC), Santiago de Compostela, Spain.
Translational Pediatrics and Infectious Diseases, Department of Pediatrics, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain.
Front Immunol. 2021 Jan 21;11:580219. doi: 10.3389/fimmu.2020.580219. eCollection 2020.
Rotavirus (RV) is an enteric pathogen that has devastating impact on childhood morbidity and mortality worldwide. The immunologic mechanism underlying the protection achieved after RV vaccination is not yet fully understood.
We compared the transcriptome of children affected by community-acquired RV infection and children immunized with a live attenuated RV vaccine (RotaTeq).
RV vaccination mimics the wild type infection causing similar changes in children's transcriptome, including transcripts associated with cell cycle, diarrhea, nausea, vomiting, intussusception, and abnormal morphology of midgut. A machine learning approach allowed to detect a combination of nine-transcripts that differentiates vaccinated from convalescent-naturally infected children (AUC: 90%; 95%CI: 70-100) and distinguishes between acute-infected and healthy control children (in both cases, AUC: 100%; 95%CI: 100-100). We identified a miRNA hsa-mir-149 that seems to play a role in the host defense against viral pathogens and may have an antiviral role.
Our findings might shed further light in the understanding of RV infection, its functional link to intussusception causes, as well as guide development of antiviral treatments and safer and more effective vaccines. The nine-transcript signature may constitute a marker of vaccine protection and helps to differentiate vaccinated from naturally infected or susceptible children.
轮状病毒（RV）是一种肠道病原体，它对全球儿童发病率和死亡率有毁灭性影响。RV 疫苗接种后获得保护的免疫机制尚未完全阐明。
我们比较了社区获得性 RV 感染儿童和接种活减毒 RV 疫苗（RotaTeq）儿童的转录组。
RV 疫苗接种模拟了野生型感染，导致儿童转录组发生类似变化，包括与细胞周期、腹泻、恶心、呕吐、肠套叠和中肠形态异常相关的转录本。机器学习方法可检测出区分接种疫苗和自然感染康复儿童的九种转录本组合（AUC：90%；95%CI：70-100），并区分急性感染和健康对照儿童（在这两种情况下，AUC：100%；95%CI：100-100）。我们鉴定了一个 miRNA hsa-mir-149，它似乎在宿主防御病毒病原体中发挥作用，可能具有抗病毒作用。
我们的发现可能进一步阐明 RV 感染的机制，其与肠套叠病因的功能联系，以及指导抗病毒治疗以及更安全有效的疫苗的开发。这九种转录本特征可能是疫苗保护的标志物，有助于区分接种疫苗和自然感染或易感儿童。
