Abstract
BackgroundRotavirus (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.MethodsWe compared the transcriptome of children affected by community-acquired RV infection and children immunized with a live attenuated RV vaccine (RotaTeq®).ResultsRV 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.DiscussionOur 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.
Highlights
Rotavirus (RV) is an enteric pathogen that has devastating impact on childhood morbidity and mortality worldwide
The vast majority of children do not experience any adverse effects after vaccination [40], we found altered expression of biomarkers associated with vomit, diarrhea, fecal incontinence, and nausea
Due to the reported association of intussusception and earlier RV vaccines in the past [risk of 1.5 [95%CI: 0.2–3.2] with the first dose according to Yih et al [41]], large safety studies were conducted on the current vaccines RV5 and RV1 before they were approved
Summary
Rotavirus (RV) is an enteric pathogen that has devastating impact on childhood morbidity and mortality worldwide. RV is one of the leading causes of infant death in developing countries; it was estimated that RV was responsible for the death of more than 600,000 children per year worldwide before the introduction of vaccines, and 128,000 after the introduction of vaccines in children younger than five years [2,3,4]. RV1 is made from a single human live attenuated strain that replicates in the intestine [3, 7]. Both vaccines confer protection and have shown real-life effectiveness and impact; the exact immunologic mechanism conferring protection against RV gastroenteritis is not fully understood [8]. It has been recently reported that RV infection is able to provoke global changes in the transcriptome of infected cells to evade the innate host response; likewise, the host develops mechanisms to avoid viral invasion, including a strong inhibition of glycophorin genes [13]
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