Effects of Iron Supplementation on Pediatric Vaccine Response (VINO)

ID/IDA affects many young children in Africa. Vaccines provide tremendous benefits in LMIC; however, they currently fail to reach their full potential. We need to better understand the causes of vaccine failure, in order to develop new strategies to improve vaccine immunogenicity.

This study will contribute to children's health by: (1) providing updated guidelines to better define the prevalence of ID/IDA in early infancy, and its safe and effective control using iron; and (2) providing a new approach to improve response to pediatric vaccines in LMIC, by ensuring adequate iron status at time of vaccination.

Study Overview

• Status: Completed
• Conditions: Iron-deficiency; Iron Deficiency Anemia; Pediatric ALL; Vaccination
• Intervention / Treatment: Dietary supplement: Iron syrup; Dietary supplement: Multivitamin syrup

Detailed Description

Two major pediatric public health goals in LMIC are increasing immunization effectiveness and reducing ID/IDA in children. ID/IDA affects many young children in Africa. Current guidelines do not recommend routine testing of hemoglobin in early infancy, as it is generally believed that most infants are born with adequate iron stores to last 6 months. However, many African infants are born with low iron stores and ID/IDA may develop earlier than generally appreciated, within 2-3 months after birth. Vaccines provide tremendous benefits in LMIC; however, they currently fail to reach their full potential. We need to better understand the causes of vaccine failure, in order to develop new strategies to improve vaccine immunogenicity. Despite lower efficacy in LMIC, these vaccines provide a major benefit because the disease burden is so high; however, if approaches can be found to improve immunogenicity, these vaccines would be even more powerful.

For this study, 6 weeks old infants will be randomly assigned to two study groups. Group 1 will receive iron at time of pediatric vaccinations from age 6-24 weeks. Group 2 will receive no iron at time of pediatric vaccinations. All infants will receive a multivitamin syrup from age 6-24 weeks. All infants remaining ID/IDA at age 24 weeks will receive iron. Infants will be followed-up until age 52 weeks.

• Study Type: Interventional
• Enrollment (Actual): 288
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Kenya
  • Kwale
    • Msambweni, Kwale, Kenya
      • Msambweni County Referral Hospital
• Switzerland
  • Zürich, Switzerland, 8092
    • Human Nutrition Laboratory ETH Zurich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 1 month (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Mother at least ≥15 years of age.
• 6 weeks (+/- 3 days) of age
• Iron deficient (erythrocyte zinc protoporphyrin (ZnPP) >61 μmol/mol heme)
• With or without anemia, but not severely anemic (Hb >70 g/L)
• No malaria
• No medical condition that precludes study involvement
• Mother HIV negative
• Vaginal delivery
• No iron supplementation prior to study enrolment
• Not wasted (length for height z score of ≥-2)
• Not underweight (weight for age z score ≥-2)
• From the hospital record, term or late preterm delivery (≥34 weeks)
• Full-time breastfed at least until the screening
• No vaccines beyond the birth dose of OPV and BCG prior to enrolment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Immediate iron treatment; Iron and multivitamin syrup	Dietary supplement: Iron syrup; Daily supplementation with iron; Dietary supplement: Multivitamin syrup; Daily supplementation with multivitamins
Placebo Comparator: Delayed iron treatment; Multivitamin syrup	Dietary supplement: Multivitamin syrup; Daily supplementation with multivitamins

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pertussis antibody profile	from 6 to 24 weeks
Diphtheria antibody profile	from 6 to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
antiviral immunoglobulin G response	Immunoassay	6 weeks of age
antiviral immunoglobulin G response	Immunoassay	24 weeks of age
infant antiviral immunoglobulin G response	Immunoassay	52 weeks of age
immune cell populations	number and type of immune cells	6 weeks of age
immune cell populations	number and type of immune cells	24 weeks of age
immune cell populations	number and type of immune cells	52 weeks of age
Proteomics	Proteins involved in immune response	6 weeks of age
Proteomics	Proteins involved in immune response	24 weeks of age
Proteomics	Proteins involved in immune response	52 weeks of age
Transcriptomics	Genes involved in immune response	24 weeks of age
Intestinal fatty acid binding protein	Gut inflammation	6 weeks of age
Intestinal fatty acid binding protein	Gut inflammation	14 weeks of age
Intestinal fatty acid binding protein	Gut inflammation	24 weeks of age
Calprotectin	Gut inflammation	6 weeks of age
Calprotectin	Gut inflammation	14 weeks of age
Calprotectin	Gut inflammation	24 weeks of age
Hemoglobin		6 weeks of age
Hemoglobin		14 weeks of age
Hemoglobin		24 weeks of age
Hemoglobin		38 weeks of age
Hemoglobin		52 weeks of age
Plasma ferritin		6 weeks of age
Plasma ferritin		14 weeks of age
Plasma ferritin		24 weeks of age
Plasma ferritin		38 weeks of age
Plasma ferritin		52 weeks of age
C-reactive protein		6 weeks of age
C-reactive protein		14 weeks of age
C-reactive protein		24 weeks of age
C-reactive protein		38 weeks of age
C-reactive protein		52 weeks of age
Alpha-glycoprotein		6 weeks of age
Alpha-glycoprotein		14 weeks of age
Alpha-glycoprotein		24 weeks of age
Alpha-glycoprotein		38 weeks of age
Alpha-glycoprotein		52 weeks of age
Plasma iron		6 weeks of age
Plasma iron		14 weeks of age
Plasma iron		24 weeks of age
Plasma iron		38 weeks of age
Plasma iron		52 weeks of age
soluble transferrin receptor		6 weeks of age
soluble transferrin receptor		14 weeks of age
soluble transferrin receptor		24 weeks of age
soluble transferrin receptor		38 weeks of age
soluble transferrin receptor		52 weeks of age
Tetanus antibody profile		from 6 to 24 weeks
Haemophilus influenzae b antibody profile		from 6 to 24 weeks
Pneumococcus antibody profile		from 6 to 24 weeks
Rotavirus antibody profile		from 6 to 24 weeks
Polio antibody profile		from 6 to 24 weeks
Anti-vaccine antibody titers		38 weeks of age
Anti-vaccine antibody titers		52 weeks of age
Anti-vaccine seroconversion		14 weeks of age
Anti-vaccine seroconversion		24 weeks of age
Anti-vaccine seroconversion		38 weeks of age
Anti-vaccine seroconversion		52 weeks of age
Anti-vaccine antibody avidity index	percentage of antibodies that remain bound to beads	14 weeks of age
Anti-vaccine antibody avidity index	percentage of antibodies that remain bound to beads	24 weeks of age
Anti-vaccine antibody avidity index	percentage of antibodies that remain bound to beads	38 weeks of age
Anti-vaccine antibody avidity index	percentage of antibodies that remain bound to beads	52 weeks of age

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Human milk oligosaccharide secretor type	secretor yes or no	14 weeks of age
Erythrocyte zinc protoporphyrin		6 weeks of age
Erythrocyte zinc protoporphyrin		14 weeks of age
Erythrocyte zinc protoporphyrin		24 weeks of age
Erythrocyte zinc protoporphyrin		38 weeks of age
Erythrocyte zinc protoporphyrin		52 weeks of age

Collaborators and Investigators

• Sponsor: Jessica Rigutto
• Collaborators: University of Oxford; Jomo Kenyatta University of Agriculture and Technology Kenya; Karolinka Institute Sweden; National Institute for Public Health and Environment Netherlands

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2021
• Primary Completion (Actual): April 3, 2023
• Study Completion (Actual): October 16, 2023

Study Registration Dates

• First Submitted: January 28, 2021
• First Submitted That Met QC Criteria: February 4, 2021
• First Posted (Actual): February 9, 2021

Study Record Updates

• Last Update Posted (Actual): January 24, 2024
• Last Update Submitted That Met QC Criteria: January 22, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Anemia, Hypochromic; Anemia; Iron Metabolism Disorders; Anemia, Iron-Deficiency; Iron Deficiencies
• Other Study ID Numbers: VINO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No