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A novel hepatitis B virus variant in the sera of immunized children
V D Karthigesu1, L M Allison, M Fortuin
1Department of Pathology and Infectious Diseases, Royal Veterinary College, London, U.K.
Insights
A new hepatitis B virus (HBV) strain was found in Gambian children despite vaccination. This novel HBV variant may evade immune responses, impacting diagnosis and prevention strategies.
Area of Science:
- Virology
- Immunology
- Public Health
Background:
- Hepatitis B virus (HBV) infection remains a global health concern.
- Vaccination is a primary strategy for HBV prevention.
- Immune escape variants pose a challenge to vaccine efficacy.
Purpose of the Study:
- To characterize a novel HBV variant detected in vaccinated children.
- To investigate the genetic and immunological implications of this variant.
Main Methods:
- Serological testing for hepatitis B surface antigen (HBsAg) and anti-HBsAg antibodies.
- Detection and sequencing of HBV DNA from patient sera.
- Comparative sequence analysis to identify genetic mutations.
Main Results:
- A novel HBV variant was identified in two vaccinated children with high antibody titers.
- The variant showed genetic relatedness to the ayw4 subtype but possessed unique mutations.
- A key mutation (Lysine to Glutamic acid at residue 141) was identified in the immunodominant 'a' determinant region of the S protein.
Conclusions:
- The identified HBV variant demonstrates potential immune escape properties.
- This finding highlights the emergence of novel HBV strains challenging vaccine-induced immunity.
- Further research is needed to assess the diagnostic and prophylactic implications of this variant.
Abstract:
A novel hepatitis B virus (HBV) variant was detected in the sera of two children in The Gambia, West Africa. The children had been immunized with plasma-derived vaccine and had developed antibody titres of 1448 international units x 10(-3) (mIU)/ml and 133 mIU/ml respectively against the hepatitis B surface antigen (HBsAg). Despite the protective levels of antibodies, HBV DNA was subsequently detected in both children. The complete surface (S) protein gene sequence demonstrated that this HBV isolate was closely related to the ayw4 subtype. However, five nucleotide changes were identified and two of these were unique to the Gambian isolate. One of these changes was within the region of the S gene coding for the immunodominant a determinant of the S protein. A unique nucleotide change from adenosine to guanosine at nucleotide 421 was found, resulting in an amino acid substitution at residue 141 from lysine to glutamic acid. Previous studies have shown that amino acids 141 to 146 are critical for binding to the protective anti-HBsAg antibodies. The presence of a variant HBV in these children suggests the emergence of a novel strain of HBV which can evade immune recognition. This has potential implications for HBV diagnosis and prophylaxis.