Haemophilus influenzae Type b Immunity After Hib Vaccination and Its Association with Serum Iron, Zinc, and Copper in Southwest Iran: Is a Vaccine Booster Needed?

Abstract

Background: Globally, vaccination has substantially reduced invasive Haemophilus influenzae type b (Hib) disease. However, limited information is available on the persistence of protective antibodies after Iran incorporated the Hib-containing pentavalent vaccine into the national immunization program in 2014. Micronutrients, including iron, zinc, and copper, may influence immune responses. Objectives: This study aimed to assess Hib-specific antibody levels and their association with trace element status in vaccine-eligible children in Jahrom, Iran. Methods: This cross-sectional study was conducted in Jahrom, southwestern Iran, from October 2024 to May 2025. Serum samples were collected from 450 children who had received the Hib-containing pentavalent vaccine after its introduction in Iran in 2014, with doses administered at 2, 4, and 6 months of age. Anti-Hib immunoglobulin G (IgG) antibody concentrations were measured using an enzyme-linked immunosorbent assay (ELISA). Results: Among 450 children, 246 (54.7%) were male, and the mean age was 78.4 ± 33.2 months. Overall, 75.6% had short-term Hib protection, and 18.7% had long-term protection. The mean serum anti-Hib antibody concentration was 0.547 ± 0.446 μg/mL. Linear regression (adjusted R2 = 0.883) showed that serum concentrations of iron (B = 0.009, P < 0.001), zinc (B = 0.001, P = 0.010), and copper (B = 0.012, P < 0.001) were positively associated with anti-Hib antibody levels. Conclusions: Following the introduction of the Hib-containing pentavalent vaccine, only 18.7% of participants had antibody titers indicating sustained protection. Micronutrients may influence vaccine-induced immunity. These findings underscore the need for rigorous surveillance and reporting of invasive Hib disease to assess the disease burden despite vaccination. The low proportion of children with long-term protective antibody levels suggests that supplemental Hib vaccination may be needed to ensure durable protection.