Effects of Oral Iron Supplementation on Vaccine Response in Iron Deficient Kenyan Women

Effects of Oral Iron Supplementation Before vs. at Time of Vaccination on Immune Response in Iron Deficient Kenyan Women

Iron deficiency (ID) anemia (IDA) is a global public health problem, with the highest prevalence in Africa. Vaccines often underperform in low- and middle- income countries (LMIC), and undernutrition, including ID, likely plays a role. Recent studies have shown the importance of iron status in vaccine response. Intravenous iron given at time of vaccination improved response to yellow fever and COVID-19 vaccines in IDA Kenyan women. Whether oral iron treatment would have a similar beneficial effect on vaccine response is uncertain. Also, timing of oral iron treatment needs further investigation.

The co-primary objectives of this study are to assess 1) whether IDA in Kenyan women impairs vaccine response, and whether oral iron treatment improves their response; 2) the timing of oral iron treatment to improve vaccine response (prior to vaccination vs at time of vaccination).

We will conduct a double-blind randomized controlled trial in southern Kenya to assess the effects of iron supplementation on response to three single-shot vaccines: Johnson & Johnson COVID- 19 (JJ COVID-19), the quadrivalent meningococcal vaccine (MenACWY) and the typhoid Vi polysaccharide vaccine (Typhim Vi). Women with IDA will be recruited and randomly assigned to three study groups: group 1 (pre- treatment) will receive 100 mg oral iron as ferrous sulfate (FeSO4) daily on days 1-56; group 2 (simultaneous treatment) will receive matching placebo daily on days 1-28, and 200 mg oral iron as FeSO4 daily on days 29-56; and group 3 (control) will receive matching placebo daily on days 1-56. Women in all groups will receive the JJ COVID-19 vaccine, the MenACWY and the Typhim Vi vaccine on day 28. Cellular immune response and serology will be measured at 28 days after vaccination in all groups.

Study Overview

• Status: Completed
• Conditions: Iron Deficiency Anemia
• Intervention / Treatment: Dietary supplement: Oral iron supplementation (pre-treatment); Biological: COVID-19 vaccine; Biological: MenACWY vaccine; Dietary supplement: Oral iron supplementation (simultaneous treatment); Biological: Typhim Vi vaccine

• Study Type: Interventional
• Enrollment (Actual): 180
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Kenya
  • Msambweni, Kenya, 80404
    • Msambweni County Referral Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Willing and able to give informed consent for participation in the trial
• Female aged 18-49 years
• Moderate anemia (Hb <110 g/L, but not severely anemic with Hb <80 g/L) • Iron deficient (ZnPP >40 mmol/mol haem)
• Anticipated residence in the study area for the study duration

Exclusion Criteria:

• Major chronic infectious disease (e.g., HIV infection);
• Major chronic non-infectious disease (e.g., Type 2 diabetes, cancer);
• Chronic medications;
• Use of iron-containing mineral and vitamin supplementation 2 weeks prior to study start;
• COVID-19 vaccine or confirmed COVID-19 infection within the past 2 years
• MenACWY vaccine in the past
• Typhoid vaccine in the past
• Pregnant (confirmed by rapid test during screening) or lactating.
• Malaria (confirmed by rapid test) à study start will be postponed

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pre-treatment group; Participants assigned to this group will receive 200 mg oral iron on alternate days on study days 1-56.	Dietary supplement: Oral iron supplementation (pre-treatment); Iron supplements as 200 mg oral iron as FeSO4 given on alternate day on days 1-56; Biological: COVID-19 vaccine; Johnson & Johnson COVID- 19 (JJ COVID-19) vaccination given on day 28 to all participants; Biological: MenACWY vaccine; MenACWY vaccination given on day 28 to all participants; Biological: Typhim Vi vaccine; Typhim Vi vaccination given on day 28 to all participants
Experimental: Simultaneous treatment group; Participants assigned to this group will receive placebo on alternate days on study days 1-28 and 200 mg oral iron on alternate days on study days 29-56.	Biological: COVID-19 vaccine; Johnson & Johnson COVID- 19 (JJ COVID-19) vaccination given on day 28 to all participants; Biological: MenACWY vaccine; MenACWY vaccination given on day 28 to all participants; Dietary supplement: Oral iron supplementation (simultaneous treatment); Iron supplements as 200 mg oral iron as FeSO4 given on alternate day on days 28-56; Biological: Typhim Vi vaccine; Typhim Vi vaccination given on day 28 to all participants
Placebo Comparator: Control group; Participants assigned to this group will receive placebo on alternate days on study days 1-56.	Biological: COVID-19 vaccine; Johnson & Johnson COVID- 19 (JJ COVID-19) vaccination given on day 28 to all participants; Biological: MenACWY vaccine; MenACWY vaccination given on day 28 to all participants; Biological: Typhim Vi vaccine; Typhim Vi vaccination given on day 28 to all participants

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
anti-spike (S1) immunoglobulin (IgG) and anti-receptor-binding domain (RBD) IgG concentrations against severe acute respiratory syndrome (SARS)-Coronavirus (COV)-2 [iU/ml]	Day 56
IgG concentration against meningococcal serogroups A, C, W, and Y (anti-MenACWY IgG) [iU/ml]	Day 56
IgG concentration against Typhoid [iU/ml]	Day 56

Secondary Outcome Measures

Outcome Measure	Time Frame
Hemoglobin concentration (g/L) at baseline	Day 1
Hemoglobin concentration (g/L) at time of vaccination	Day 28
Hemoglobin concentration (g/L) at study end	Days 56
Zinc protoporphyrin concentration (µmol/mol heme) at baseline	Day 1
Zinc protoporphyrin concentration (µmol/mol heme) at time of vaccination	Day 28
Zinc protoporphyrin concentration (µmol/mol heme) at study end	Day 56
Plasma iron concentration (µg/mL) at baseline	Day 1
Plasma iron concentration (µg/mL) at time of vaccination	Day 28
Plasma iron concentration (µg/mL) at study end	Day 56
Total iron binding capacity at baseline	Day 1
Total iron binding capacity at time of vaccination	Day 28
Total iron binding capacity at study end	Day 56
Transferrin saturation (%) at baseline	Day 1
Transferrin saturation (%) at time of vaccination	Day 28
Transferrin saturation (%) at study end	Day 56
Plasma ferritin concentration (µg/L) at baseline	Day 1
Plasma ferritin concentration (µg/L) at time of vaccination	Day 28
Plasma ferritin concentration (µg/L) at study end	Day 56
Soluble transferrin receptor concentration (mg/L) at baseline	Day 1
Soluble transferrin receptor concentration (mg/L) at time of vaccination	Day 28
Soluble transferrin receptor concentration (mg/L) at study end	Day 56
C-reactive protein concentration (mg/L) at baseline	Day 1
C-reactive protein concentration (mg/L) at time of vaccination	Day 28
C-reactive protein concentration (mg/L) at study end	Day 56
Retinol binding protein concentration (µmol/L) at baseline	Day 1
Retinol binding protein concentration (µmol/L) at time of vaccination	Day 28
Retinol binding protein concentration (µmol/L) at study end	Day 56
Alpha-glycoprotein (AGP) concentration at baseline	Day 1
Alpha-glycoprotein concentration (g/L) at time of vaccination	Day 28
Alpha-glycoprotein concentration (g/L) at study end	Day 56
T-cell response assessed with an enzyme-linked immunosorbent assay (ELISA) detecting IFN-gamma produced by CD4+ and CD8+ T cell responses to SARS-CoV-2 peptides at study end	Day 56
COVID-19 specific T cell response measured in peripheral blood mononuclear cells by ELISpot assay quantifying specific cytokines' concentration.	Day 56
Typhim Vi specific B-cell response measured in peripheral blood mononuclear cells by ELISpot assay quantifying antibodies' and memory B cell concentration.	Day 56

Collaborators and Investigators

• Sponsor: Nicole Stoffel
• Collaborators: University of Oxford; Swiss Federal Institute of Technology
• Investigators: Principal Investigator: Simon Karanja, PhD, JKUAT

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2023
• Primary Completion (Actual): July 16, 2024
• Study Completion (Actual): July 16, 2024

Study Registration Dates

• First Submitted: June 7, 2023
• First Submitted That Met QC Criteria: June 16, 2023
• First Posted (Actual): June 26, 2023

Study Record Updates

• Last Update Posted (Actual): December 26, 2025
• Last Update Submitted That Met QC Criteria: December 19, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Anemia; Iron deficiency; Vaccine response; Women of reproductive age
• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Iron Metabolism Disorders; Anemia, Hypochromic; Nutritional and Metabolic Diseases; Hemic and Lymphatic Diseases; Iron Deficiencies; Anemia; Anemia, Iron-Deficiency; Biological Products; Complex Mixtures; Vaccines; Viral Vaccines; COVID-19 Vaccines; Vi polysaccharide vaccine, typhoid
• Other Study ID Numbers: DIVA_II

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