Envelope protein variability among HBV-Infected asymptomatic carriers and immunized children with breakthrough infections

• Published in: Journal of medical virology Vol. 80; no. 9; pp. 1537 - 1546
• Main Authors: Mendy, Maimuna, D'Mello, Felicity, Kanellos, Theophanis, Oliver, Stefan, Whittle, Hilton, Howard, Colin R
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.09.2008; Wiley-Liss
• Subjects: Adolescent; Adult; Amino Acid Substitution - genetics; Biological and medical sciences; breakthrough infections; Carrier State - epidemiology; Carrier State - immunology; Carrier State - virology; Child; Child, Preschool; DNA, Viral - blood; Fundamental and applied biological sciences. Psychology; Gambia - epidemiology; Hepatitis B - epidemiology; Hepatitis B - immunology; Hepatitis B - virology; Hepatitis B Surface Antigens - blood; hepatitis B surface mutants; Hepatitis B virus; Hepatitis B virus - genetics; Hepatitis B virus - immunology; Hepatitis B virus - isolation & purification; hepatocellular carcinoma; Human viral diseases; Humans; Infant; Infectious diseases; Medical sciences; Microbiology; Miscellaneous; Molecular Sequence Data; Mutation, Missense; Phylogeny; Sequence Analysis, DNA; Viral diseases; Viral Envelope Proteins - genetics; Viral Envelope Proteins - immunology; Virology; Gambia; Human; Immunization; Orthohepadnavirus; Hepatic disease; Hepatocellular carcinoma; Asymptomatic; Malignant tumor; Protein; Infection; Virus; Viral hepatitis B; breakthrough infections; hepatitis B surface mutants; Hepadnaviridae; Viral disease; Digestive diseases; Mutation; Hepatitis B virus; Child; Cancer
• ISSN: 0146-6615; 1096-9071; 1096-9071
• DOI: 10.1002/jmv.21221

A detailed study of hepatitis B virus (HBV) surface variants and their role in breakthrough infections has been conducted in The Gambia, West Africa. Samples from 1856 vaccinated subjects were tested for hepatitis B surface antigen (HBsAg). Evidence of infection was found in 11% (22/192) of subjects with breakthrough infections and 18 (81.8%) were also positive for HBV DNA following PCR analysis. A cohort of 58 unvaccinated carriers which also included 11 patients with hepatocellular carcinoma was also investigated in order to establish the prevalence of surface variants in the unvaccinated population. Analysis of the S gene from HBV PCR-positive subjects (n = 64) revealed little variation in the S gene of these subjects. Twenty-four S protein sequences (37.5%) were identical and a further 22 sequences differed by only a single amino acid. The K141E variant found in previous work was not detected and little variation was observed in the immunodominant "a" determinant; a single change was found in one vaccinated patient (Q129H) and nine changes detected among six unvaccinated carriers. This study showed that breakthrough HBV infection in vaccinated Gambians is mainly caused by the wild type genoytype E strain and that immune escape mutants are uncommon. However, HBV mutants may play a role in establishing infection later in life when anti-HBs antibodies have begun to decline. Further investigation is required to determine the cause of these breakthrough infections and whether they contribute to the establishment of the carrier state. J. Med. Virol. 80:1537-1546, 2008.