Characteristics of hepatitis B virus surface protein and occult hepatitis B infection in infants with immunoprophylaxis failure from Indonesia

Vaccine. 2025 May 22:56:127130. doi: 10.1016/j.vaccine.2025.127130. Epub 2025 Apr 29.

Abstract

Perinatal hepatitis B virus (HBV) infection carries a significant risk of chronicity and complications while making infected people reservoirs for further transmission. Hepatitis B immunization in infants, with or without hepatitis B immune globulin (HBIG), has proven effective in preventing mother-to-child transmission. Nevertheless, some newborns of mothers with high viremia testing positive for hepatitis B e antigen (HBeAg) may not benefit from HBV immunoprophylaxis. Nineteen (10.2 %) of 186 infants born to HBV-infected mothers were HBV DNA-positive. HBV genotypes, serotypes, and hepatitis B surface antigen (HBsAg) sequences were comparable in most mother-cord blood-infant sample pairings, indicating that the infants' HBV strains originated from their mothers. Three (15.3 %) infants had overt HBV infection, whereas 16 (84.2 %) had occult HBV infection (OBI). The HBV isolates from infants exhibited 26 mutations: 38.5 % in the 'a' determinant and 61.5 % in the rest of HBsAg. Mutations were identified in B-cell and T-cell epitopes, impairing humoral and cellular responses to detect or neutralize the virus. This rendered immunoprophylaxis and diagnostics ineffective while inducing tolerance to the infection. HBV strains with these mutations can persist and cause complications, but they can be transmitted undetected by HBsAg tests commonly used in community healthcare. This study reveals the risk of HBV transmission from HBsAg mutant-infected mothers to newborns despite having received the birth dose with HBIG and complete hepatitis B vaccination.

Keywords: Hepatitis B; Hepatitis B immune globulin; Hepatitis B vaccine; Immunoprophylaxis; Mother-to-child transmission; Occult hepatitis B; Vaccination; Vaccine escape mutants.

MeSH terms

  • Adult
  • DNA, Viral / blood
  • DNA, Viral / genetics
  • Female
  • Genotype
  • Hepatitis B Antibodies
  • Hepatitis B Surface Antigens* / genetics
  • Hepatitis B Surface Antigens* / immunology
  • Hepatitis B Vaccines / administration & dosage
  • Hepatitis B Vaccines / immunology
  • Hepatitis B virus* / classification
  • Hepatitis B virus* / genetics
  • Hepatitis B virus* / immunology
  • Hepatitis B virus* / isolation & purification
  • Hepatitis B* / epidemiology
  • Hepatitis B* / immunology
  • Hepatitis B* / prevention & control
  • Hepatitis B* / transmission
  • Humans
  • Indonesia / epidemiology
  • Infant
  • Infant, Newborn
  • Infectious Disease Transmission, Vertical* / prevention & control
  • Male
  • Mutation
  • Pregnancy
  • Treatment Failure

Substances

  • Hepatitis B Surface Antigens
  • Hepatitis B Vaccines
  • DNA, Viral
  • Hepatitis B Antibodies