1. Host Transcriptomic Response Following Administration of Rotavirus Vaccine in Infants' Mimics Wild Type Infection.
- Author
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Gómez-Carballa A, Barral-Arca R, Cebey-López M, Currás-Tuala MJ, Pischedda S, Gómez-Rial J, Habgood-Coote D, Herberg JA, Kaforou M, Martinón-Torres F, and Salas A
- Subjects
- Child, Disease Resistance genetics, Humans, Infant, Machine Learning, MicroRNAs genetics, Sequence Analysis, RNA, Transcriptome, Vaccination, Vaccines, Attenuated immunology, Community-Acquired Infections immunology, Rotavirus immunology, Rotavirus Infections immunology, Rotavirus Vaccines immunology
- 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., Competing Interests: FM-T has received honoraria from GSK, Pfizer, Sanofi Pasteur, MSD, Seqirus, and Janssen for taking part in advisory boards and expert meetings, and for acting as speaker in congresses outside the scope of the submitted work. JG-R has received honoraria from GSK, Pfizer, and MSD for taking part in advisory boards and expert meetings, and for acting as speaker in congresses outside the scope of the submitted work. FM-T has also acted as principal investigator in RCTs of the above-mentioned companies as well as Ablynx, Regeneron, Roche, Abbott, Novavax, and MedImmune, with honoraria paid to his institution. The remaining authors declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gómez-Carballa, Barral-Arca, Cebey-López, Currás-Tuala, Pischedda, Gómez-Rial, Habgood-Coote, Herberg, Kaforou, Martinón-Torres and Salas.)- Published
- 2021
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