Studies of Acute and Memory Immune Responses to Orally Administered Vaccines in Developing Country Children and Factors That May Augment Such Responses
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 1,016
- 试验地点
- 1
- 主要终点
- 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
研究概览
简要总结
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.
详细描述
Research Design and Methods
Vaccine field sites and overall study design:
Mirpur. The vaccine studies will be carried out at the field site in Mirpur, in urban Dhaka, where oral cholera, ETEC and rotavirus studies as well as amoebiasis studies are being conducted over the last 15 years . For the Dukoral vaccine, two doses will be given to the study participants, 14 days apart. In case of Vivotif, 3 doses will be administered on alternate days i.e. days 1, 3 and 5 or in two doses 28 days apart.
Blood and stool samples will be collected prior to vaccination, and 7 days after intake of each dose of the cholera vaccine and 7 days after the intake of last dose of typhoid vaccine, and the volumes to be sampled for immunological assays have been described in Appendix 2. The participants will not be allowed to eat or drink from one hour before and one hour after intake of the vaccine. To assess the effect of zinc on immune response to typhoid vaccine in young children, supplementation will be initiated 2 weeks before the first dose and will continue up to 21 days after the last (third) dose of typhoid vaccine (that is for a total of 40 days).
Serum zinc concentrations will be determined at baseline only. Venous blood will be collected in trace element free vacutainers, which will be placed in ice until arrival at the ICDDR,B laboratory the same day.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 1 Year 至 45 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Placebo (Drug)
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
干预措施: Placebo (Drug)
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.
干预措施: Control (Other)
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.
干预措施: Zinc Sulphate (Drug)
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
干预措施: Albendazole and Secnidazole (Drug)
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.
干预措施: Arsenic (Other)
结局指标
主要结局
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
时间窗: 3 years
次要结局
- Determine the acute and memory B and T cell responses to oral cholera and typhoid vaccine in children and adults(3 Years)