Evaluation of the G145R Mutant of the Hepatitis B Virus as a Minor Strain in Mother-to-Child Transmission

Abstract

The role of the hepatitis B virus (HBV) mutant G145R, with a single change in amino acid 145 of the surface protein, as a minor population remains unknown in mother-to-child transmission. The minor strain as well as the major strain of the G145R mutant were evaluated in three cohorts using a locked nucleic acid probe-based real-time PCR. The breakthrough cohort consisted of children who were born to HBV carrier mothers and became HBV carriers despite immnoprophylaxis (n = 25). The control cohort consisted of HBV carriers who had no history of receiving the hepatitis B vaccine, hepatitis B immunoglobulin or antiviral treatment (n = 126). The pregnant cohort comprised pregnant women with chronic HBV infection (n = 31). In the breakthrough cohort, 6 showed positive PCR results (major, 2; minor, 4). In the control cohort, 13 showed positive PCR results (major, 0; minor, 13). HBeAg-positive patients were prone to have the G145R mutant as a minor population. Deep sequencing was performed in a total of 32 children (PCR positive, n = 13; negative, n = 19). In the breakthrough cohort, the frequency of the G145R mutant ranged from 0.54% to 6.58%. In the control cohort, the frequency of the G145R mutant ranged from 0.42% to 4.1%. Of the 31 pregnant women, 4 showed positive PCR results (major, n = 0; minor, n = 4). All of the pregnant women were positive for HBeAg and showed a high viral load. Three babies born to 3 pregnant women with the G145R mutant were evaluated. After the completion of immunoprophylaxis, 2 infants became negative for HBsAg. The remaining infant became negative for HBsAg after the first dose of HB vaccine. G145R was detected in one-fourth of the children with immunoprophylaxis failure. However, the pre-existence of the G145R mutant as a minor population in pregnant women does not always cause breakthrough infection in infants.

Horizontal Transmission of Hepatitis B Virus From Mother to Child Due to Immune Escape Despite Immunoprophylaxis

“…Reports of vaccine breakthrough, or more accurately, “failure to clear infection” (1), in infants or children is infrequent following complete immunoprophylaxis, but has been associated with intrauterine or perinatal exposure to the virus (2) or in rare cases, evolution and expansion of isolates having mutations within the viral genome resulting in escape from neutralization by antibodies elicited to the vaccine or present in immunoglobulin (ie, immune escape; (3)). These immune escape mutations are often transmitted from the mother or they may emerge as de novo mutations (1), although studies have shown that infants born to mothers having HBV immune escape mutations successfully respond to vaccination and are protected against infection (4). A glycine to arginine substitution at amino acid 145 (G145R) within the antigenic determinant of the hepatitis B surface antigen (HBsAg) protein (aa 124–147) is the most common mutation described to result in immune escape following vaccination (5,6).…”

Analysis of Hepatitis B virus (HBV) mutations in patients from Western Saudi Arabia with chronic disease

“…Another mutation in the S gene is the G145R, which is reported to play an important role as a vaccine escape mutant. This mutation is located in the "a" determinant region (aa124-147) and is known to be the most virulent mutant in breakthrough infections [43,44]. In our study, only the wild type was detected in all of the sequenced cases.…”

Cross-Protection of Hepatitis B Vaccination among Different Genotypes

“…The major vaccine escape mutants reported in Taiwan [ 122 , 123 , 124 , 125 , 126 , 127 ], Japan [ 128 , 129 , 130 , 131 , 132 ], Singapore [ 133 ], England, Wales [ 134 ], China [ 135 , 136 ], Pacific Islands [ 137 ] and Indonesia [ 138 ] are shown in Table 2 . In addition to the prototype G145R, other S-gene mutations (alone or in combination) that might escape neutralizing anti-HBs have been identified worldwide ( Table 2 ) [ 123 , 125 ].…”