Studies of Immune Responses to Orally Administered Vaccines in Developing Country

NCT01019083 | Completed Phase 1 DMC

• 1 other identifier: 2007-066
• Study Type: interventional
• Target: 1,016
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cholera; Typhoid

Keywords

Cholera; Typhoid; Oral Vaccine; Immune response; Vaccine Evaluation; Nutrition; Child Health

Outcome Measures

Primary Outcomes (1)

• 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

  3 years

Secondary Outcomes (1)

• Determine the acute and memory B and T cell responses to oral cholera and typhoid vaccine in children and adults

  3 Years

Study Arms (6)

zinc supplementation-Placebo

PLACEBO COMPARATOR

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

Anti Parasite Drug- Placebo

PLACEBO COMPARATOR

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

Effect of Arsenic in Dukoral- Control

EXPERIMENTAL

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

zinc supplementation

EXPERIMENTAL

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

administration of antiparasitic drugs

EXPERIMENTAL

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

Effect of arsenic on Dukoral response

EXPERIMENTAL

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

Interventions

Placebo DRUG

Placebo will be given according to randomization list

Also known as: Zinc Sulphate

zinc supplementation-Placebo

Control OTHER

Control will be selected from the Arsenic non contaminated Area

Also known as: Arsenic Contaminated Area

Effect of Arsenic in Dukoral- Control

Zinc Sulphate DRUG

Zinc Sulphate will be given according to randomization list

Also known as: Placebo

zinc supplementation

Albendazole and Secnidazole DRUG

Albendazole and Secnidazole will be given according to randomization list

Also known as: Placebo

administration of antiparasitic drugs

Arsenic OTHER

Participant will be selected from the Arsenic Contaminated Area

Also known as: Non contaminated Arsenic area

Effect of arsenic on Dukoral response

Eligibility Criteria

• Age: 1 Year - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• history of chronic gastrointestinal disorder.
• 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.
• any febrile illness in the preceding week.
• other chronic illness.
• history of receiving antibiotic treatment within the last 7 day.
• 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.

Sponsors & Collaborators

• International Centre for Diarrhoeal Disease Research, Bangladesh: lead
• Göteborg University: collaborator

Study Sites (1)

Firdausi Qadri

Dhaka, 1212, Bangladesh

Location

Related Publications (2)

• Qadri F, Ahmed T, Wahed MA, Ahmed F, Bhuiyan NA, Rahman AS, Clemens JD, Black RE, Albert MJ. Suppressive effect of zinc on antibody response to cholera toxin in children given the killed, B subunit-whole cell, oral cholera vaccine. Vaccine. 2004 Jan 2;22(3-4):416-21. doi: 10.1016/j.vaccine.2003.07.005.

  PMID: 14670323 BACKGROUND

• Ahmed T, Svennerholm AM, Al Tarique A, Sultana GN, Qadri F. Enhanced immunogenicity of an oral inactivated cholera vaccine in infants in Bangladesh obtained by zinc supplementation and by temporary withholding breast-feeding. Vaccine. 2009 Feb 25;27(9):1433-9. doi: 10.1016/j.vaccine.2008.12.036. Epub 2009 Jan 13.

  PMID: 19146904 BACKGROUND

MeSH Terms

Conditions

Cholera; Typhoid Fever

Interventions

Zinc Sulfate; Albendazole; secnidazole; Arsenic

Condition Hierarchy (Ancestors)

Vibrio Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Salmonella Infections; Enterobacteriaceae Infections

Intervention Hierarchy (Ancestors)

Sulfates; Sulfuric Acids; Sulfur Acids; Sulfur Compounds; Inorganic Chemicals; Zinc Compounds; Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Metalloids; Elements

Study Officials

• Firdausi Qadri, PhD

  International Centre for Diarrhoeal Disease Research, Bangladesh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: November 22, 2009
• First Posted: November 25, 2009
• Study Start: February 1, 2008
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: July 12, 2011

Record last verified: 2009-11

Locations

BA (1)