title: Low detection rate and maternal provenance of hepatitis B virus S gene mutants in cases of failed postnatal immunoprophylaxis in England and Wales.
abstract: Hepatitis B virus (HBV) infection occurred despite full passive-active immunoprophylaxis in 20 of 321 infants born to mothers seropositive for hepatitis B e antigen. In 2 (12%) of 17 infected infants, mother-infant DNA sequence mismatches were found in a segment of the HBV S gene coding for antigenic determinants of the HBV surface antigen (HBsAg) amplified from sera by polymerase chain reaction (PCR). Point substitutions occurred in codons 120, 134, and 144 of the HBsAg polypeptide in the variant sequence of 1 infant and in codon 126 in the other; all were missense mutations. Mutant sequences could not be recovered from maternal sera by PCR cloning but were selectively generated using an amplification refractory mutation system. The frequency of potential vaccine escape mutants is therefore low, and these preexist maternally as minor variants.
authors.affiliation: Virus Reference Division, Central Public Health Laboratory, Communicable Disease Surveillance Centre, London, United Kingdom.
authors.forename: S L
authors.initials: SL
authors.lastname: Ngui
authors.forename: S
authors.initials: S
authors.lastname: O'Connell
authors.forename: R P
authors.initials: RP
authors.lastname: Eglin
authors.forename: J
authors.initials: J
authors.lastname: Heptonstall
authors.forename: C G
authors.initials: CG
authors.lastname: Teo
mesh_terms: D000595:Amino Acid Sequence; D003062:Codon; D005260:Female; D006509:Hepatitis B / Q000517:prevention & control*; D006514:Hepatitis B Surface Antigens / Q000235:genetics*; D006801:Humans; D007116:Immunization, Passive; D007136:Immunoglobulins / Q000276:immunology; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D011247:Pregnancy
chemical_list: D003062:Codon; D006514:Hepatitis B Surface Antigens; D007136:Immunoglobulins; C045213:hepatitis B hyperimmune globulin