The influence of human genetic variation on early transcriptional responses and protective immunity following immunization with Rotarix vaccine in infants in Ho Chi Minh City in Vietnam : a study protocol for an open single-arm interventional trial [awaiting peer review]
| Autor: | M Cong Danh, H Thi Ngoc Thu, N Nguyet Hang, Chau Nguyen Van Vinh, H Pham Thu Hien, Evelyne Kestelyn, N Thi Tuyet Hanh, G. Thwaites, L Lan Vi, T My Phuc, P Thi Hai Chau, L Dai, Stephen Baker, L Phuong Thao, Thomas C. Darton, T Doan Hao, L Quan Thinh, P Thi Thanh Tam, N Thi Mong Tuyen, C Anderson, N Thi En, B Thi Thuy Tien, B Yu Hang Bai, N Le Thi Quynh, T Thi Ngoc Dung, V Thi Ngoc Diep, R. de Alwis, L Thi Hanh, L Thanh Hoang Nhat, H Van Hien, H Thi Thuy Trang, T Anh Dao, V Thi Huyen Diu, H Thi Diem Tuyet, N Thi Thuy Linh, N Thi Thu Hong, N Thi Thanh Nhan |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Pediatrics medicine.medical_specialty viruses Population Medicine (miscellaneous) medicine.disease_cause General Biochemistry Genetics and Molecular Biology law.invention 03 medical and health sciences 0302 clinical medicine Randomized controlled trial law Rotavirus Medicine 030212 general & internal medicine education education.field_of_study business.industry virus diseases biochemical phenomena metabolism and nutrition Vaccine efficacy digestive system diseases Vaccination 030104 developmental biology Immunization business Vaccine failure Blood sampling |
| Zdroj: | Wellcome Open Research |
| Popis: | Background: Rotavirus (RoV) remains the leading cause of acute gastroenteritis in infants and children aged under five years in both high- and low-middle-income countries (LMICs). In LMICs, RoV infections are associated with substantial mortality. Two RoV vaccines (Rotarix and Rotateq) are widely available for use in infants, both of which have been shown to be highly efficacious in Europe and North America. However, for unknown reasons, these RoV vaccines have markedly lower efficacy in LMICs. We hypothesize that poor RoV vaccine efficacy across in certain regions may be associated with genetic heritability or gene expression in the human host. Methods/design: We designed an open-label single-arm interventional trial with the Rotarix RoV vaccine to identify genetic and transcriptomic markers associated with generating a protective immune response against RoV. Overall, 1,000 infants will be recruited prior to Expanded Program on Immunization (EPI) vaccinations at two months of age and vaccinated with oral Rotarix vaccine at two and three months, after which the infants will be followed-up for diarrheal disease until 18 months of age. Blood sampling for genetics, transcriptomics, and immunological analysis will be conducted before each Rotarix vaccination, 2-3 days post-vaccination, and at each follow-up visit (i.e. 6, 12 and 18 months of age). Stool samples will be collected during each diarrheal episode to identify RoV infection. The primary outcome will be Rotarix vaccine failure events (i.e. symptomatic RoV infection despite vaccination), secondary outcomes will be antibody responses and genotypic characterization of the infection virus in Rotarix failure events. Discussion: This study will be the largest and best powered study of its kind to be conducted to date in infants, and will be critical for our understanding of RoV immunity, human genetics in the Vietnam population, and mechanisms determining RoV vaccine-mediated protection. Registration: ClinicalTrials.gov, ID: NCT03587389. Registered on 16 July 2018. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|