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Mutations in the 'a' determinant of hepatitis B surface antigen among Chinese infants receiving active postexposure
1Department of Molecular Virology, Shanghai Medical University, People's Republic of China.
Insights
Hepatitis B vaccine failure in infants was studied. Mutations in the hepatitis B surface antigen
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- Hepatitis B virus (HBV) infection remains a global health concern.
- Postexposure prophylaxis with plasma-derived hepatitis B vaccine is crucial for preventing maternal-infant transmission.
- Breakthrough HBV infections despite vaccination highlight the need to understand underlying mechanisms.
Purpose of the Study:
- To investigate mutations in the 'a' determinant of hepatitis B surface antigen (HBsAg) in infants who failed postexposure immunization.
- To assess the impact of these mutations on vaccine efficacy and HBV transmission.
Main Methods:
- Serum samples from 24 infants with breakthrough HBsAg positivity were analyzed.
- Polymerase chain reaction (PCR) was used to amplify and sequence the 'a' determinant region (Nucleotides 419-598) of HBsAg.
- Nucleotide mutations and resulting amino acid substitutions were identified and analyzed.
Main Results:
- Four out of 24 infants (16.7%) exhibited mutations in the 'a' determinant region, leading to amino acid substitutions.
- One case (N1) showed a glycine to arginine substitution at codon 145 (145R), with the mother co-infected with wild-type and mutant HBV.
- The 145R variant was transient in N1, with only wild-type virus detected five years later.
- No significant correlation was found between mutation rate and anti-HBs antibody response post-vaccination.
Conclusions:
- Mutations in the HBsAg 'a' determinant, including the 145R variant, are not a primary cause of hepatitis B vaccine failure in preventing maternal-infant transmission in this cohort.
- The 145R variant appears unstable and less prevalent without immune selective pressure.
- Further research is needed to fully elucidate the complex factors contributing to vaccine breakthrough infections.
Abstract:
Twenty-four infants who became positive to the surface antigen of hepatitis B virus (HBsAg) despite a complete course of active postexposure immunization with plasma derived hepatitis B vaccine were studied. The polymerase chain reaction amplified products of the common neutralizing epitope 'a' determinant of HBsAg (Nucleotide 419-598) from serum samples were sequenced and analyzed for nucleotide mutations. Four cases (16.7%) had mutations that led to amino acid substitutions between codons 124 and 147. Only one case (N1) showed a substitution at codon 145 (from glycine to arginine, 145R), the other three were at codons 126-129. The mother of N1 was co-infected with the wild type and the mutant virus. Five years later, serum of N1 showed only the wild type virus. There was no significant relationship between the mutation rate and the anti-HBs response to hepatitis B vaccination. Results suggest that without immune selective pressure, 145R variant was not frequently observed, and was not stable. Mutation in the 'a' determinant was not an important cause of failure to prevent maternal-infant transmission of HBV by active postexposure hepatitis B immunization in Chinese children.