Association between anaemia, micronutrient status, and pneumococcal vaccine responses in young Kenyan children

Introduction: Anaemia and micronutrient deficiencies are common in low- and middle-income countries, where vaccine-induced immune responses are often suboptimal. However, whether pre-vaccination nutritional status influences pneumococcal vaccine immunogenicity in young children remains poorly characterised. Methods: We examined associations between pneumococcal vaccine responses in 670 Kenyan children enrolled in three vaccine trials: PRISM (PCV10; n=195; NCT01028326), FPCV (fractional- and full-dose PCV10/PCV13; n=306; NCT03489018), and PATH-wSP (whole-cell pneumococcal vaccine; n=169; NCT02543892) and baseline anaemia (FPCV and PATH-wSP) and micronutrient status (iron, folate, zinc, and vitamins A, B12, D, and E). Analyses were performed separately for each trial. Primary outcomes were post-vaccination serotype- or antigen-specific IgG concentrations, opsonophagocytic activity (OPA) titres, and composite IgG or OPA z scores. Results: Vitamin B12 and haemoglobin concentrations were positively associated with composite and serotype- or antigen-specific antibody responses in analyses controlling for age, sex, malnutrition and inflammation. In the PRISM trial, PCV10-induced IgG (serotypes 1 and 6B) and OPA (serotypes 1, 4, 14, and 23F) responses were positively associated with vitamin B12 concentrations. Moderate anaemia was associated with lower IgG responses to serotypes 9V and 14 following full-dose PCV13 vaccination (FPCV) and lower antigen-specific IgG responses following the 1 mg PATH-wSP vaccine. No consistent associations were observed for ferritin, folate, zinc, or vitamins A, D, and E. Conclusion: Vitamin B12 deficiency and anaemia were associated with reduced pneumococcal vaccine responses in young Kenyan children. Optimising nutritional status before vaccination could be a strategy to improve vaccine responses in populations where anaemia and micronutrient deficiencies are common.