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Studies of Immune Responses to Orally Administered Vaccines in Developing Country

This study has been completed.
Sponsor:
Collaborator:
Göteborg University
Information provided by:
International Centre for Diarrhoeal Disease Research, Bangladesh
ClinicalTrials.gov Identifier:
NCT01019083
First received: November 22, 2009
Last updated: July 11, 2011
Last verified: November 2009
  Purpose

The efficacy and immunogenicity of enteric vaccines have generally been found to be lower in children in the developed than in the developing countries. This has been observed with vaccines against cholera rotavirus, ETEC and typhoid vaccines. There are a number of factors that may contribute to such differences in vaccine "take rates" in children, e.g. breast feeding and nutritional status of the children might influence their immunogenicity and efficacy. Thus, breast feeding of newborn and young infants may adversely influence the immune response to vaccination, which might have more pronounced effect in developing than in developed countries. Breastfeeding has also been shown to interfere with the serum immune responses to rotavirus vaccine although this effect could be overcome by administering three rather than one dose of the oral rotavirus vaccine. Our recent study of Dukoral in Bangladeshi children aged 18 months or younger has shown that the response rates and the magnitude of responses improved when breast milk was temporarily withheld . Thus, administration of vaccines may have to be adjusted when given to breast fed children. Another factor that may affect the immunogenicity is the effect of zinc. Previous studies have shown that zinc enhances the immune response to cholera vaccine in participants > 2 years of age , a recent study also observed a similar effect in infants.

In this research project, we plan to study a number of different factors that might influence the immunogenicity of the two licensed oral model vaccines, specifically the inactivated killed oral cholera vaccine, Dukoral, and the live oral typhoid vaccine, Ty21a. We will also identify strategies that might improve the immunogenicity of the vaccines. The main objective of our study is to identify immunization regimens that may improve the immunogenicity of the vaccines in young children, which could be subsequently in field trials in Bangladesh and other developing countries. Specifically, we will determine if: (i) interventions identified to enhance immune responses to Dukoral, including zinc supplementation, could also enhance the immune responses to Ty21a; (ii) these two vaccines are able to induce both acute and memory B and T cell responses, (iii) treatment with antiparasitic drugs prior to immunization could modulate the immune responses to cholera and typhoid vaccines; and (iv) examine if arsenic exerts a suppressive effect on the immunogenicity of these vaccines.


Condition Intervention Phase
Cholera
Typhoid
Drug: Placebo
Other: Control
Drug: Zinc Sulphate
Drug: Albendazole and Secnidazole
Other: Arsenic
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: Studies of Acute and Memory Immune Responses to Orally Administered Vaccines in Developing Country Children and Factors That May Augment Such Responses

Resource links provided by NLM:


Further study details as provided by International Centre for Diarrhoeal Disease Research, Bangladesh:

Primary Outcome Measures:
  • Determine if the immunogenicity of typhoid (Vivotif) and cholera vaccine (Dukoral) in young children is influenced by the factors i. zinc supplementation ii. antiparasitic drugs and iii. relationship between serum arsenic and immune response to Dukoral [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Determine the acute and memory B and T cell responses to oral cholera and typhoid vaccine in children and adults [ Time Frame: 3 Years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 1016
Study Start Date: February 2008
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: zinc supplementation-Placebo
Determine if the immunogenicity of oral typhoid can be enhanced in children by introducing zinc supplementation: Our recent studies on the interactions of oral cholera vaccine with breast milk and zinc provide some basis for improving immunogenicity, but additional work is needed to improve many of the oral vaccines. In this study we also plan to evaluate if the immune response to Cholera and Vivotif can be enhanced by supplementation with zinc using methods described earlier. We would like to study children, 2-5 years of age for this purpose.
Drug: Placebo
Placebo will be given according to randomization list
Other Name: Zinc Sulphate
Placebo Comparator: Anti Parasite Drug- Placebo
There is a high burden of enteric parasites in the gut of people living in densely populated areas of less developed countries. The effect of concurrent parasitic infestations on immune responses has not been studied widely, although it is an area of utmost importance for natural protection as well as vaccine immuno-prophylaxis. In this study we plan to determine the impact of pretreatment with antiparasitic agents (albendazole and secnidazole) on the immunogenicity of the oral cholera and typhoid vaccines in children, 2-5 years of age
Drug: Placebo
Placebo will be given according to randomization list
Other Name: Albendazole and Senidazole
Experimental: Effect of Arsenic in Dukoral- Control
In this study, we aim to evaluate if immunogenicity of the oral cholera vaccine is modified in children living in a high arsenic contaminated area in Bangladesh. The plan is to study children 2-5 year old living in Shahrasti thana near Matlab where the tubewell water is highly contaminated with arsenic and this study will not be randomized double-blind, and compare their responses with responses of age matched children living in arsenic free area, such as in Mirpur area of Dhaka city. We only plan to study the effect of Dukoral vaccinees since this vaccine has been widely studied in Bangladesh. If an impact of arsenic is seen on immune response to this vaccine, future studies could be done with other vaccines including Vivotif.
Other: Control
Control will be selected from the Arsenic non contaminated Area
Other Name: Arsenic Contaminated Area
Experimental: zinc supplementation
Determine if the immunogenicity of oral typhoid can be enhanced in children by introducing zinc supplementation: Our recent studies on the interactions of oral cholera vaccine with breast milk and zinc provide some basis for improving immunogenicity, but additional work is needed to improve many of the oral vaccines. In this study we also plan to evaluate if the immune response to Cholera and Vivotif can be enhanced by supplementation with zinc using methods described earlier. We would like to study children, 2-5 years of age for this purpose.
Drug: Zinc Sulphate
Zinc Sulphate will be given according to randomization list
Other Name: Placebo
Experimental: administration of antiparasitic drugs
There is a high burden of enteric parasites in the gut of people living in densely populated areas of less developed countries. The effect of concurrent parasitic infestations on immune responses has not been studied widely, although it is an area of utmost importance for natural protection as well as vaccine immuno-prophylaxis. In this study we plan to determine the impact of pretreatment with antiparasitic agents (albendazole and secnidazole) on the immunogenicity of the oral cholera and typhoid vaccines in children, 2-5 years of age
Drug: Albendazole and Secnidazole
Albendazole and Secnidazole will be given according to randomization list
Other Name: Placebo
Experimental: Effect of arsenic on Dukoral response
In this study, we aim to evaluate if immunogenicity of the oral cholera vaccine is modified in children living in a high arsenic contaminated area in Bangladesh. The plan is to study children 2-5 year old living in Shahrasti thana near Matlab where the tubewell water is highly contaminated with arsenic and this study will not be randomized double-blind, and compare their responses with responses of age matched children living in arsenic free area, such as in Mirpur area of Dhaka city. We only plan to study the effect of Dukoral vaccinees since this vaccine has been widely studied in Bangladesh. If an impact of arsenic is seen on immune response to this vaccine, future studies could be done with other vaccines including Vivotif.
Other: Arsenic
Participant will be selected from the Arsenic Contaminated Area
Other Name: Non contaminated Arsenic area

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   1 Year to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. voluntary written informed consent will be obtained from the parent/guardians for participation of children including their vaccination and sampling of blood and stool for various assays.
  2. healthy children (1 - 5 years)and adults (18-45 years) both males and females living in the Mirpur field site, who are not currently enrolled in any other research study, whether conducted by ICDDR,B or other organization, will be screened and enrolled subject to meeting the eligibility criteria. For Dukoral study that will be conducted in Shahrasti we will recruit only 2-5 years old children.

Exclusion Criteria:

  1. history of chronic gastrointestinal disorder.
  2. diarrheal illness in the past 2 weeks (diarrhea defined as passage of 3 or more abnormally loose or watery stool in a 24 hour period.
  3. any febrile illness in the preceding week.
  4. other chronic illness.
  5. history of receiving antibiotic treatment within the last 7 day.
  6. severe protein energy malnutrition (PEM). The nutritional status of the children will be assessed using anthropometric measurements (weight-for-age, and weight-for-length/height); children below -2SD for weight for height/length of the NCHS median will not be enrolled. Similarly, children who have received zinc in the past two months will also not be recruited.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01019083

Locations
Bangladesh
Firdausi Qadri
Dhaka, Bangladesh, 1212
Sponsors and Collaborators
International Centre for Diarrhoeal Disease Research, Bangladesh
Göteborg University
Investigators
Principal Investigator: Firdausi Qadri, PhD International Centre for Diarrhoeal Disease Research, Bangladesh
  More Information

Publications:
Responsible Party: Dr. Firdausi Qadri, International Centre for Diarrhoeal Disease Research, Bangladesh
ClinicalTrials.gov Identifier: NCT01019083     History of Changes
Other Study ID Numbers: 2007-066
Study First Received: November 22, 2009
Last Updated: July 11, 2011
Health Authority: Bangladesh: Ethical Review Committee

Keywords provided by International Centre for Diarrhoeal Disease Research, Bangladesh:
Cholera
Typhoid
Oral Vaccine
Immune response
Vaccine Evaluation
Nutrition
Child Health

Additional relevant MeSH terms:
Cholera
Bacterial Infections
Gram-Negative Bacterial Infections
Vibrio Infections
Albendazole
Antiparasitic Agents
Secnidazole
Zinc
Zinc Sulfate
Anthelmintics
Anti-Infective Agents
Anticestodal Agents
Antimitotic Agents
Antineoplastic Agents
Antiplatyhelmintic Agents
Antiprotozoal Agents
Astringents
Dermatologic Agents
Growth Substances
Micronutrients
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Trace Elements
Tubulin Modulators

ClinicalTrials.gov processed this record on November 25, 2014