Alberto Gómez-Carballa1,2,3, Ruth Barral-Arca1,2,3, Miriam Cebey-López1,2,3, Maria José Currás-Tuala1,2,3, Sara Pischedda1,2,3, José Gómez-Rial1,3, Dominic Habgood-Coote4, Jethro A Herberg4, Myrsini Kaforou4, Federico Martinón-Torres1,2, Antonio Salas1,3. 1. 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. 2. Translational Pediatrics and Infectious Diseases, Department of Pediatrics, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain. 3. Unidade de Xenética, Instituto de Ciencias Forenses (INCIFOR), Facultade de Medicina, Universidade de Santiago de Compostela, and GenPoB Research Group, Instituto de Investigacinó Sanitaria (IDIS), Hospital Clínico Universitario de Santiago (SERGAS), Santiago de Compostela, Spain. 4. Section of Pediatric Infectious Diseases, Imperial College London, London, United Kingdom.
Abstract
Background: 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. Methods: We compared the transcriptome of children affected by community-acquired RV infection and children immunized with a live attenuated RV vaccine (RotaTeq®). Results: 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. Discussion: 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.
Background: 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. Methods: We compared the transcriptome of children affected by community-acquired RV infection and children immunized with a live attenuated RV vaccine (RotaTeq®). Results: 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 infectedchildren (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. Discussion: 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.
Authors: A Salas; J Pardo-Seco; M Cebey-López; J M Martinón-Martínez; J Gómez-Rial; M J Currás-Tuala; S Pischedda; R Barral-Arca; A Justicia-Grande; I Rivero-Calle; J Vilar; F Martinón-Torres Journal: Vaccine Date: 2019-05-04 Impact factor: 3.641
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Authors: Ruth Barral-Arca; Alberto Gómez-Carballa; Miriam Cebey-López; María José Currás-Tuala; Sara Pischedda; Sandra Viz-Lasheras; Xabier Bello; Federico Martinón-Torres; Antonio Salas Journal: Int J Mol Sci Date: 2020-04-15 Impact factor: 5.923
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Authors: Sara Pischedda; Irene Rivero-Calle; Alberto Gómez-Carballa; Miriam Cebey-López; Ruth Barral-Arca; Jose Gómez-Rial; Jacobo Pardo-Seco; María-José Curras-Tuala; Sandra Viz-Lasheras; Xabier Bello; Ana B Crujeiras; Angel Diaz-Lagares; María Teresa González-López; Federico Martinón-Torres; Antonio Salas Journal: Front Immunol Date: 2022-05-10 Impact factor: 8.786