How Gut Health Affects Immune Responses to the Oral Rotavirus Vaccine in Adults in Zambia (Rota-Omics)

June 2, 2026 updated by: Centre for Infectious Disease Research in Zambia

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Estimated)

43

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Zambia
    • Lusaka Province
      • Lusaka, Lusaka Province, Zambia, P.O.BOX34681LUSAKA,ZAMBIA10101
        • Recruiting
        • TROPGAN
        • Contact:
        • Principal Investigator:
          • Paul Kelly, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Healthy adults living in Chawama, a densely populated peri-urban setting in proximity to the study recruitment site.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Consenting healthy adult Participants aged ≥ 18 years and ≤ 50 years
Participants will receive a double oral Rotarix dose at baseline. Serial duodenal biopsies will be collected from predefined subgroups to capture early, mid, and late mucosal responses while minimizing per-participant invasive procedures (the sparse sampling design allows construction of profiles of responses over 4 time points while no individual participant undergoes more than 2 endoscopies). The study design avoids confounding from placebo-related procedural differences and allows for robust within-subject longitudinal comparisons.
Biological: Rotarix®,
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of participants completing all scheduled study procedures
Time Frame: Through study completion, an average of 1 year.
The percentage of enrolled participants who complete all scheduled study visits and protocol-defined procedures.
Through study completion, an average of 1 year.
Sample Quality Control (QC) Success Rate
Time Frame: Through 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).
Through study completion, an average of 1 year.
Proportion of intestinal biopsy samples meeting predefined quality control thresholds
Time Frame: Through 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.
Through study completion, an average of 1 year.
Pre-analytical Sample Processing Efficiency
Time Frame: Periprocedural
The 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.
Periprocedural

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Follow-up Retention Rate
Time Frame: Through 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.
Through study completion, an average of 1 year.
Regulated Gene Expression Profiles
Time Frame: Baseline, 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.
Baseline, and up to 52 weeks post-enrollment.
Correlation of Mucosal Spatial Transcriptomics with Systemic Immunity
Time Frame: Baseline, 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.
Baseline, and up to 52 weeks post-enrollment.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre for Infectious Disease Research in Zambia

Collaborators

Bill and Melinda Gates Foundation

Investigators

  • Principal Investigator: Michelo Simuyandi, Master's Degree (MSc), Centre for Infectious Disease Research in Zambia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 30, 2026

Primary Completion (Estimated)

September 30, 2026

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

May 18, 2026

First Submitted That Met QC Criteria

June 2, 2026

First Posted (Actual)

June 4, 2026

Study Record Updates

Last Update Posted (Actual)

June 4, 2026

Last Update Submitted That Met QC Criteria

June 2, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 7400-2025

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Due to requirements of the ethics committee, the study is not permitted to share individual participant data unless otherwise requested for and approved by the University of Zambia Biomedical Research Ethics Committee.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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