Studies of Immune Responses to Orally Administered Vaccines in Developing Country
Status:
Completed
Trial end date:
2010-12-01
Target enrollment:
Participant gender:
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
Details
Lead Sponsor:
International Centre for Diarrhoeal Disease Research, Bangladesh