Hepatitis B Virus Vaccine–Induced Cell-Mediated Immunity Correlates with Humoral Immune Response following Primary Vaccination during Infancy

Abstract

Data on hepatitis B virus (HBV) vaccine–induced cell-mediated immunity (CMI) and humoral immune response during infancy is scarce. We assessed HBV vaccine–induced CMI among infants stratified as nonresponders (Ab against HBV surface Ag [anti-HBs] levels <10 IU/l), low-responders (anti-HBs levels 10–100 IU/l), and high-responders (anti-HBs levels ≥100 IU/l) following their primary vaccination against HBV. Moreover, we assessed the association between HBV vaccine–induced CMI and anti-HBs levels. Infants were immunized with HBV vaccine at ages 2, 4, and 6 mo. Hepatitis B surface Ag (HBsAg)-specific proliferation, intracellular cytokine production, and bulk cytokine secretion were assessed on PBMCs collected at 1 y and anti-HBs levels were measured at 1 and 2 y of age. Infants classified at 2 y of age as low-responders (n = 28) had lower median levels of secreted IFN-γ than high-responders (n = 29), 17.15 pg/ml versus 33.16 pg/ml, respectively, p = 0.009. Infants classified at 2 y of age as nonresponders (n = 15) had lower median levels of secreted TNF-α than high-responders (n = 29), 116.11 pg/ml versus 162.27 pg/ml, respectively, p = 0.032. There was a positive correlation between HBsAg-specific secreted IFN-γ levels at 1 y and anti-HBs levels at 1 and 2 y of age, rho = 0.269 and 0.302, respectively, (p = 0.019 and p = 0.01, respectively). There was a positive correlation between anti-HBs levels at age 1 y and the levels of secreted IL-10, rho = 0.297, p = 0.009. HBsAg-specific IFN-γ, IL-10, and TNF-α secretion correlated with HBV vaccine–induced humoral immune response. Assessment of CMI is a useful adjunct in demonstrating the persistence of HBV vaccine–induced memory immune response.