Studies of Immune Responses to Orally Administered Vaccines in Developing Country

• Status: Completed
• Trial end date: 2010-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: International Centre for Diarrhoeal Disease Research, Bangladesh
• Collaborator: Göteborg University
• Treatments: Albendazole; Antiparasitic Agents; Metronidazole; Secnidazole; Vaccines; Zinc; Zinc Sulfate

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.