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Development of a Live Attenuated Rotavirus Vaccine as a Human Infection Challenge Model

NCT04123119 · Status: COMPLETED · Phase: NA · Type: INTERVENTIONAL · Enrollment: 22

Last updated 2019-10-14

No results posted yet for this study

Summary

The impact of licensed rotavirus vaccines in LMICs is limited by their lower immunogenicity and efficacy in these settings. Improved vaccines and vaccination schedules would result in substantially greater reductions in infant diarrhoeal disease and mortality. Placebo-controlled trials of new rotavirus vaccines are no longer ethical, leading to challenges for traditional routes of licensure for vaccines that are in the development pipeline.

A HIC model of rotavirus would address these challenges, whilst also offering an opportunity to study the causes of poor oral vaccine immunogenicity. Rotarix™ is in routine use in Zambia administered at 6 and 10 weeks infant age. Shedding of rotavirus vaccine after vaccination has recently been explored as a measure of mucosal immunity, analogous to oral poliovirus vaccine challenge models.

We propose to explore methodological development of an attenuated vaccine as a HIC model to advance rotavirus immunology and vaccinology in Zambian infants. We will evaluate use of minimally invasive procedures including sublingual/submandibular sampling and stool collection for viral shedding as measures of vaccine-induced and naturally acquired mucosal immunity. This approach holds the potential to develop the first rotavirus HIC model in a low-income country and could be used to accelerate licensure of new rotavirus vaccines and explore causes of poor oral vaccine efficacy as well as correlates of vaccine protection.

To do this, we will recruit a cohort of 22 Zambian infants receiving Rotarix™ at 6 and 10 weeks as part of their routine immunisation. Infants will be followed up actively on the day of vaccination, days 1,3,5 and 7 following each vaccine dose for collection of stool and saliva samples. Blood samples for IgA and IgG titres will be collected on days 0, 28, 31 and 56, and standard ELISA methods used to determine vaccine seroconversion.

The work brings together collaborators at the Centre for Infectious Disease Research in Zambia, Imperial College in UK and Christian Medical College, Vellore in India to prepare the Zambian centre as a potential HIC model site.

Conditions

  • Diarrhoeal Disease

Interventions

BIOLOGICAL

Rotavirus vaccine

An exploratory and observational cohort study following infants receiving two standard doses of live, attenuated, oral Rotarix™ administered at 6 \& 10 weeks.

Sponsors & Collaborators

  • Imperial College London

    collaborator OTHER

  • Christian Medical College, Vellore, India

    collaborator OTHER

  • Centre for Infectious Disease Research in Zambia

    lead OTHER

Principal Investigators

  • Roma Chilengi, MBCHB · Centre for Infectious Disease Research in Zambia

Study Design

Allocation
NA
Purpose
PREVENTION
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
6 Weeks
Max Age
8 Weeks
Sex
ALL
Healthy Volunteers
Yes

Timeline & Regulatory

Start
2019-01-22
Primary Completion
2019-05-10
Completion
2019-05-10

Countries

  • Zambia

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT04123119 on ClinicalTrials.gov