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How Gut Health Affects Immune Responses to the Oral Rotavirus Vaccine in Adults in Zambia

Temporal and Spatial Immune Profiling of Oral Rotavirus Vaccine Responses in Zambian Adults With Environmental Enteropathy

Status
Recruiting
Phases
Unknown
Study type
Observational
Source
ClinicalTrials.gov
Registry ID
NCT07626606
Acronym
Rota-Omics
Enrollment
43
Registered
2026-06-04
Start date
2026-03-30
Completion date
2026-12-31
Last updated
2026-06-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Feasibility Study, Rota Virus Gastroenteritis, Transcriptomics, Vaccine Immune Response

Keywords

Transcriptomics, Feasibility, Microbiome, Immunity, Rotavirus, Vaccine

Brief summary

The Rotavirus SpatioTrasncriptomics (Rota-Omics) study is a multidisciplinary research project aimed at understanding why oral rotavirus vaccines perform less effectively in some low- and middle-income countries, including Zambia. Rotavirus remains one of the leading causes of severe diarrheal disease in infants and young children worldwide, despite the widespread introduction of vaccines such as Rotarix® and Rotavac®. Although these vaccines have greatly reduced childhood deaths in many countries, vaccine effectiveness is often lower in settings where the burden of disease is highest. Understanding the reasons behind this reduced protection is critical for improving child health globally. A major focus of the study is Environmental Enteropathy (EE), also known as Environmental Enteric Dysfunction (EED), a chronic inflammatory condition of the small intestine that is common in low-resource settings. EE is associated with damage to the intestinal lining, chronic immune activation, poor nutrient absorption, and impaired gut barrier function. These changes are thought to interfere with the body's ability to respond effectively to oral vaccines, which rely on strong intestinal immune responses. The RotaOmics study uses a systems biology approach to investigate how the immune system, gut microbiome, nutrition, and intestinal inflammation interact to influence rotavirus vaccine responses. The term "omics" refers to advanced technologies that allow researchers to study genes, proteins, microbes, and other biological processes at a large scale. By combining these approaches, the study aims to identify biological markers and immune pathways associated with strong or weak vaccine responses. The study involves the collection of samples such as blood, stool, saliva, and breast milk from mothers and infants at different time points before and after vaccination. These samples are analysed using laboratory methods including antibody testing, molecular pathogen detection, microbiome sequencing, and immune profiling. The study also evaluates markers of gut inflammation and intestinal health. One important goal of the project is to identify correlates of protection, which are measurable biological indicators that predict whether a vaccine is likely to protect against disease. Identifying these markers could help guide the development of improved vaccines or supportive interventions to enhance vaccine performance in vulnerable populations. The study also contributes to a broader understanding of mucosal immunity, which refers to immune responses occurring in the gastrointestinal tract. Since many enteric infections begin in the gut, understanding intestinal immune function is important not only for rotavirus vaccines but also for other oral vaccines and diarrheal diseases. In addition to its scientific objectives, RotaOmics includes a strong capacity-building component. The project supports training for local scientists, clinicians, and laboratory personnel in areas such as molecular biology, immunology, genomics, bioinformatics, and data analysis. By strengthening local research expertise and infrastructure, the study aims to support long-term scientific development and improve regional capacity for infectious disease research and outbreak response. Overall, the RotaOmics study seeks to generate new insights into why oral rotavirus vaccines underperform in some settings and to identify strategies that may improve vaccine effectiveness and child health outcomes in Zambia and similar regions worldwide.

Interventions

BIOLOGICALRotarix®,

This is an infant vaccine, but this study participants in this study will receive a double oral Rotarix dose at baseline as per study design.

Sponsors

Centre for Infectious Disease Research in Zambia
Lead SponsorOTHER
Bill and Melinda Gates Foundation
CollaboratorOTHER

Study design

Observational model
COHORT
Time perspective
PROSPECTIVE

Eligibility

Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes

Inclusion criteria

* Age ≥ 18 years and ≤ 50 years. * Able and willing to provide written informed consent. * Reside within Lusaka district and available for scheduled follow-up. * Willing to undergo two endoscopy procedures with serial sample collection.

Exclusion criteria

* Pregnant or breastfeeding. * Active gut disease requiring treatment (e.g., active peptic ulcer disease, gastrointestinal bleeding). * Known severe immunodeficiency (HIV with CD4 \< 200 cells/mm³, current cancer chemotherapy, systemic corticosteroids equivalent to \>20 mg/day prednisolone for \>2 weeks). * Severe comorbidities rendering endoscopy unsafe (e.g., severe cardiopulmonary disease, uncontrolled hypertension, oropharyngeal abnormalities). * Use of anticoagulants where suspension is unsafe or unwillingness to withhold anticoagulation when clinically indicated. * Receipt of any live vaccine within 30 days prior to enrolment or planned live vaccine within 30 days after Rotarix administration. * Any condition judged by the investigator to compromise participant safety or data integrity. * Participants who had a recent diarrhoea episode, or who have taken NSAID drugs or antibiotics, will be eligible for re-assessment after a month without this disqualifier. Pregnancy testing and counselling: Women of reproductive potential will require a negative urine pregnancy test within 24 hours prior to endoscopy and vaccination and will be counselled to avoid pregnancy during the first 30 days post-vaccination.

Design outcomes

Primary

MeasureTime frameDescription
Proportion of participants completing all scheduled study proceduresThrough study completion, an average of 1 year.The percentage of enrolled participants who complete all scheduled study visits and protocol-defined procedures.
Sample Quality Control (QC) Success RateThrough study completion, an average of 1 year.The proportion of tissue biopsies that successfully meet the defined technical quality control thresholds required for spatial transcriptomic (ST) processing (e.g., RNA integrity number, tissue structural preservation, and spot sequencing depth).
Proportion of intestinal biopsy samples meeting predefined quality control thresholdsThrough study completion, an average of 1 year.The percentage of collected intestinal biopsy samples meeting predefined quality control criteria for downstream laboratory analysis, including tissue integrity and adequate sample preservation.
Pre-analytical Sample Processing EfficiencyPeriproceduralThe precise duration of time (measured in minutes) recorded from the exact moment of clinical biopsy collection to the successful snap-freezing/cryopreservation of the tissue sample.

Secondary

MeasureTime frameDescription
Clinical Follow-up Retention RateThrough study completion, an average of 1 year.The percentage of enrolled study participants who successfully complete all scheduled follow-up clinical visits and specimen collection time points as per the study protocol.
Regulated Gene Expression ProfilesBaseline, and up to 52 weeks post-enrollment.Identification of differentially expressed genes and pathway spatial modules within histologically mapped regions of interest (ROIs) on Hematoxylin and Eosin-stained tissue architectures, analysed via spatially aware linear mixed-effects models.
Correlation of Mucosal Spatial Transcriptomics with Systemic ImmunityBaseline, and up to 52 weeks post-enrollment.The statistical relationship (evaluated using Spearman rank correlation coefficients) between tissue-based spatial gene module scores and external serologic or stool-based mucosal immune biomarkers, adjusted for age, sex, and baseline environmental enteric dysfunction (EED) markers.

Countries

Zambia

Contacts

CONTACTMichelo Simuyandi, Post Graduate (MSc)
michelo.simuyandi@cidrz.org+260968424794
CONTACTStanley Mwale, Master's Degree (MPH)
stanley.mwale@cidrz.org+260966745554
PRINCIPAL_INVESTIGATORMichelo Simuyandi, Master's Degree (MSc)

Centre for Infectious Disease Research in Zambia

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Jun 5, 2026