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Published on: June 5, 2020
Hepatitis B Virus Immunization and Neonatal Acquisition of Persistent Infection in England and Wales
Shoshanna May1, Sema Mandal2, Philip Keel2
1Blood Borne Virus Unit, Virus Reference Department, National Infection Service, Public Health England, London.
Insights
Hepatitis B virus (HBV) breakthrough infections in infants may be linked to changes in the hepatitis B surface antigen (HBsAg) due to immune selection during mother-to-infant transmission. Higher maternal viral load is also a significant factor.
Area of Science:
- Virology
- Immunology
- Pediatrics
Background:
- Perinatal transmission of Hepatitis B virus (HBV) poses a risk for infant infection, with 2-5% developing chronic infection despite early immunization.
- Investigating factors contributing to HBV vaccine breakthrough infections in infants born to infected mothers is crucial for public health.
Purpose of the Study:
- To identify factors associated with persistent Hepatitis B virus (HBV) infections in infants despite timely immunization.
- To analyze alterations in hepatitis B surface antigen (HBsAg) sequence and antigenicity in mother-infant pairs with HBV transmission.
Main Methods:
- Analyzed 69 samples from HBV-infected infants (2003-2015) for serological and molecular markers.
- Utilized sequencing and epitope phenotyping to examine HBsAg alterations in infants and mothers.
- Compared viral load in maternal samples from transmitting versus non-transmitting mothers.
Main Results:
- 37% of infants had viral amino acid changes in the HBsAg "a" determinant, with 13% showing altered antigenicity.
- Higher maternal viral load (30-fold) was observed in mothers who transmitted HBV.
- Complete vaccine and hepatitis B immune globulin uptake was noted in most infants.
Conclusions:
- Immune selection during mother-to-infant HBV transmission can alter HBsAg antigenicity, potentially contributing to immunization failure.
- Maternal viral load appears to be a critical factor in HBV transmission and breakthrough infections.
- Ongoing surveillance of hepatitis B vaccine efficacy is essential to address persistent challenges.
Background:
It is believed that between 2% and 5% of infants born to hepatitis B virus (HBV)-infected mothers at a high risk of perinatal transmission will become persistently infected despite immunization starting at birth. We investigated factors associated with breakthrough infections.
Methods:
Sixty-nine samples from HBV-infected infants born between 2003 and 2015 were tested for HBV serological and molecular markers. Sequencing and epitope phenotyping were used to investigate alterations in hepatitis B surface antigen (HBsAg) sequence and antigenicity in infants and in mothers known to have transmitted and not to have transmitted virus to their infants.
Results:
Vaccine/hepatitis B immune globulin uptake was complete in the majority of HBV-infected infants. A minority (8 [12%]) had detectable plasma antibody to HBsAg at 12 months. Twenty-five of 68 (37%) infants harbored a virus with amino acid changes in the HBsAg "a" determinant, of which 13 displayed altered HBsAg antigenicity. Viral load was 30-fold higher in maternal samples from those who transmitted.
Conclusions:
Our data provide evidence to suggest that immune selection drives change at mother-infant transmission, resulting in the alteration of HBsAg antigenicity. These changes may play a role in immunization failure, but other factors including viral load may be more important. Continued monitoring of vaccine efficacy is essential.
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