No response to hepatitis B vaccine in infants born to HBsAg(+) mothers is associated to the transplacental transfer of HBsAg

Abstract

Background: No or low hepatitis B (HB) vaccine response is more frequent in infants from HBsAg(+) mothers than those from HBsAg(−). Our previous study found temporary positivity of HBsAg in infants from HBsAg(+) mothers. In this study, we hypothesized that HBsAg in infant blunt immune response to standard hepatitis B vaccination.

Methods: A total of 328 consecutive HBsAg(+) mothers and their offspring were enrolled. Blood samples were taken from mothers and their infants and quantified for HBsAg, anti-HBs titer and HBV DNA load concentration; Placenta samples were collected to stain for HBsAg.

Results: First, 6.7% infants (22/328) showed anti-HBs titer lower than 10 mIU/mL after HB vaccination (non-response to HB vaccine). HBsAg(+) newborns showed higher risk of non-response than HBsAg(−) infants (13.0% versus 5.0%, p = 0.016). Infants from high HBsAg titer mothers displayed higher risk of HBsAg positivity at birth than those from low titer mothers (45.3% versus 2.8%, p < 0.001). HBsAg titer in mothers of HBsAg(+) newborns was much higher than mothers of HBsAg(−) newborns (p < 0.001). All those data supported HBsAg can be transferred through placenta. Our hypothesis was further reinforced by immunostaining with specific antibody against HBsAg, a substantial higher prevalence (87.5% versus 30.8%, p = 0.024) and stronger immunostaining (p = 0.008) was demonstrated in HBsAg(+) group comparing with placenta of the HBsAg(−) group.

Conclusion: No response to HB vaccine in infants of HBsAg(+) mothers was associated to the transplacental transfer of HBsAg.

Keywords:

• HBsAg
• immune response
• hepatitis B vaccine
• placenta

Acknowledgements

The authors appreciate the guidance provided by Professor Shulin Zhang of Medical College of Xi’an Jiaotong University.

Disclosure statement

The authors declare no other funding or conflicts of interest relating to the publication of this manuscript.

Additional information

Funding

This study was supported by grants from the Fundamental Research Funds for the Central Universities, National Natural Science Foundation of Shaanxi Province [2015JM8404], the National Natural Science Foundation of China [Nos. 30700712 and 81670537], the Major National Science and Technology Projects for Infectious Diseases (13th Five Year, China) [No. 2016ZX10002010-1].