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 Coronavirus disease 2019 (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 the participants' response; 2) the timing of oral iron treatment to improve vaccine response (prior to vaccination vs at time of vaccination). The investigators will conduct a double-blind randomized controlled trial in southern Kenya to assess the effects of iron supplementation on response to two single-shot vaccines: Johnson & Johnson COVID- 19 (JJ COVID-19) and the quadrivalent meningococcal vaccine (MenACWY). Women with IDA will be recruited and randomly assigned to three study groups: group 1 (pre- treatment) will receive 200 mg oral iron as ferrous sulfate (FeSO4) on alternate days on days 1-56; group 2 (simultaneous treatment) will receive matching placebo on alternate days on days 1-28, and 200 mg oral iron as FeSO4 on alternate days on days 29-56; and group 3 (control) will receive matching placebo on alternate days on days 1-56. Women in all groups will receive the JJ COVID-19 vaccine and the MenACWY vaccine on day 28. Cellular immune response will be measured at 7 days after vaccination and serology will be measured at 28 days after vaccination in all groups.

Participants assigned to this group will receive 200 mg oral iron on alternate days on study days 1-56.

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.

Baseline anti-strike (S1) immunoglobulin (IgG) and anti-receptor-binding domain (RBD) IgG concentrations against severe acute respiratory syndrome (SARS)-Coronavirus (COV)-2

T-cell response assessed with an enzyme-linked immunosorbent assay (ELISA) detecting interferon-gamma (IFN-gamma) produced by T-helper cells (CD4+) and cytotoxic T cells (CD8+) responses to SARS-CoV-2 peptides at one week from vaccination

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

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 Pregnant (confirmed by rapid test during screening) or lactating. Malaria (confirmed by rapid test) à study start will be postponed