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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
180
Iron supplements as 200 mg oral iron as FeSO4 given on alternate day on days 1-56
Johnson \& Johnson COVID- 19 (JJ COVID-19) vaccination given on day 28 to all participants
MenACWY vaccination given on day 28 to all participants
Iron supplements as 200 mg oral iron as FeSO4 given on alternate day on days 28-56
Typhim Vi vaccination given on day 28 to all participants
Msambweni County Referral Hospital
Msambweni, Kenya
anti-spike (S1) immunoglobulin (IgG) and anti-receptor-binding domain (RBD) IgG concentrations against severe acute respiratory syndrome (SARS)-Coronavirus (COV)-2 [iU/ml]
Time frame: Day 56
IgG concentration against meningococcal serogroups A, C, W, and Y (anti-MenACWY IgG) [iU/ml]
Time frame: Day 56
IgG concentration against Typhoid [iU/ml]
Time frame: Day 56
Hemoglobin concentration (g/L) at baseline
Time frame: Day 1
Hemoglobin concentration (g/L) at time of vaccination
Time frame: Day 28
Hemoglobin concentration (g/L) at study end
Time frame: Days 56
Zinc protoporphyrin concentration (µmol/mol heme) at baseline
Time frame: Day 1
Zinc protoporphyrin concentration (µmol/mol heme) at time of vaccination
Time frame: Day 28
Zinc protoporphyrin concentration (µmol/mol heme) at study end
Time frame: Day 56
Plasma iron concentration (µg/mL) at baseline
Time frame: Day 1
Plasma iron concentration (µg/mL) at time of vaccination
Time frame: Day 28
Plasma iron concentration (µg/mL) at study end
Time frame: Day 56
Total iron binding capacity at baseline
Time frame: Day 1
Total iron binding capacity at time of vaccination
Time frame: Day 28
Total iron binding capacity at study end
Time frame: Day 56
Transferrin saturation (%) at baseline
Time frame: Day 1
Transferrin saturation (%) at time of vaccination
Time frame: Day 28
Transferrin saturation (%) at study end
Time frame: Day 56
Plasma ferritin concentration (µg/L) at baseline
Time frame: Day 1
Plasma ferritin concentration (µg/L) at time of vaccination
Time frame: Day 28
Plasma ferritin concentration (µg/L) at study end
Time frame: Day 56
Soluble transferrin receptor concentration (mg/L) at baseline
Time frame: Day 1
Soluble transferrin receptor concentration (mg/L) at time of vaccination
Time frame: Day 28
Soluble transferrin receptor concentration (mg/L) at study end
Time frame: Day 56
C-reactive protein concentration (mg/L) at baseline
Time frame: Day 1
C-reactive protein concentration (mg/L) at time of vaccination
Time frame: Day 28
C-reactive protein concentration (mg/L) at study end
Time frame: Day 56
Retinol binding protein concentration (µmol/L) at baseline
Time frame: Day 1
Retinol binding protein concentration (µmol/L) at time of vaccination
Time frame: Day 28
Retinol binding protein concentration (µmol/L) at study end
Time frame: Day 56
Alpha-glycoprotein (AGP) concentration at baseline
Time frame: Day 1
Alpha-glycoprotein concentration (g/L) at time of vaccination
Time frame: Day 28
Alpha-glycoprotein concentration (g/L) at study end
Time frame: 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
Time frame: Day 56
COVID-19 specific T cell response measured in peripheral blood mononuclear cells by ELISpot assay quantifying specific cytokines' concentration.
Time frame: Day 56
Typhim Vi specific B-cell response measured in peripheral blood mononuclear cells by ELISpot assay quantifying antibodies' and memory B cell concentration.
Time frame: Day 56
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