Transplacentally acquired maternal antibody against hepatitis B surface antigen in infants and its influence on the response to hepatitis B vaccine

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Abstract

Background: Passively acquired maternal antibodies in infants may inhibit active immune responses to vaccines. Whether maternal antibody against hepatitis B surface antigen (anti-HBs) in infants may influence the long-term immunogenicity of hepatitis B vaccine remains unknown. Methodology/Principal Findings: Totally 338 pairs of mothers and children were enrolled. All infants were routinely vaccinated against hepatitis B based on 0-, 1- and 6-month schedule. We characterized the transplacental transfer of maternal anti-HBs, and compared anti-HBs response in children of mothers with or without anti-HBs. In a prospective observation, all 63 anti-HBs positive mothers transferred anti-HBs to their infants; 84.1% of the infants had higher anti-HBs concentrations than their mothers. One and half years after vaccination with three doses of hepatitis B vaccine, the positive rate and geometric mean concentration (GMC) of anti-HBs in 32 infants with maternal anti-HBs were comparable with those in 32 infants without maternal antibody (90.6% vs 87.5%, P = 0.688, and 74.5 vs 73.5 mIU/ml, P = 0.742, respectively). In a retrospective analysis, five and half years after vaccination with three doses vaccine, the positive rates of anti-HBs in 88 children of mothers with anti-HBs ≥1000 mIU/ml, 94 children of mothers with anti-HBs 10-999 mIU/ml, and 61 children of mothers with anti-HBs <10 mIU/ml were 72.7%, 69.2%, and 63.9% (P = 0.521), respectively; anti-HBs GMC in these three groups were 38.9, 43.9, and 31.7 mIU/ml (P = 0.726), respectively. Conclusions/Significance: The data demonstrate that maternal anti-HBs in infants, even at high concentrations, does not inhibit the long-term immunogenicity of hepatitis B vaccine. Thus, current hepatitis B vaccination schedule for infants will be still effective in the future when most infants are positive for maternal anti-HBs due to the massive vaccination against hepatitis B. © 2011 Wang et al.

Figures

  • Figure 1. Flow diagram of study subjects. A, prospective cohort; B, retrospective cohort. HBsAg, hepatitis B surface antigen; a-HBs, antibody against HBsAg; a-HBc, antibody against hepatitis B core antigen. doi:10.1371/journal.pone.0025130.g001
  • Figure 2. Correlation of transplacentally transferred anti-HBs in infants with the maternal antibody (linear regression analysis, y = 1.393x237.286, r = 0.992, P,0.001, n = 63). doi:10.1371/journal.pone.0025130.g002
  • Table 1. Comparison of anti-HBs between infants and mothers.
  • Figure 3. Anti-HBs IgG subclasses in paired mother-infant sera. 1, 2, 3, and 4 under the X axial indicate the subclasses IgG1, G2, G3, and G4, respectively. Sera 018 and 020 were from mothers recovered from natural HBV infection, while sera 141 and 166 were from vaccinated mothers. The data from 4 paired sera were used to represent anti-HBs IgG subclasses distribution in 20 paired mother/infant sera. doi:10.1371/journal.pone.0025130.g003
  • Figure 4. Neutralization of HBsAg by paired mother-infant sera. An HBsAg positive serum from a hepatitis B patient was preincubated with each of paired sera, and the unneutralized HBsAg was detected with enzyme immunoassay. The inhibition (%) was calculated by the following formula: ([OD450 of HBsAg preincubated with anti-HBs negative serum2OD450 of HBsAg preincubated with anti-HBs]/OD450 of HBsAg preincubated with anti-HBs negative serum)6100. Anti-HBs titers in mother serum samples 1–21 were 6613, 2644, 992, 944, 611, 565, 492, 369, 352, 318, 273, 244, 149, 148, 116, 73, 44, 36, 29, 18, and 16 mIU/ml, respectively; those in cord serum samples 1–21 were 9663, 2870, 1568, 1106, 798, 766, 616, 348, 590, 525, 255, 271, 194, 147, 291, 67, 57, 103, 31, 22, and 20 mIU/ml, respectively. doi:10.1371/journal.pone.0025130.g004
  • Table 2. Anti-HBs titers in children after vaccination with three hepatitis B vaccine doses.
  • Table 3. Long-term immune response after vaccination against hepatitis B in children born to mothers with various anti-HBs levels.

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Wang, Z., Zhang, S., Luo, C., Wu, Q., Liu, Q., Zhou, Y. H., & Hu, Y. (2011). Transplacentally acquired maternal antibody against hepatitis B surface antigen in infants and its influence on the response to hepatitis B vaccine. PLoS ONE, 6(9). https://doi.org/10.1371/journal.pone.0025130

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