Vaccine- and Hepatitis B Immune Globulin-Induced Escape Mutations of Hepatitis B Virus Surface Antigen

Abstract

Hepatitis B virus surface antigen (HBsAg) vaccination has been shown to be effective in preventing hepatitis B virus (HBV) infection. The protection is based on the induction of anti-HBs antibodies against a major cluster of antigenic epitopes of HBsAg, defined as the ‘a’ determinant region of small HBsAg. Prophylaxis of recurrent HBV infection in patients who have undergone liver transplantation for hepatitis B-related end-stage liver disease is achieved by the administration of hepatitis B immune globulins (HBIg) derived from HBsAg-vaccinated subjects. The anti-HBs-mediated immune pressure on HBV, however, seems to go along with the emergence and/or selection of immune escape HBV mutants that enable viral persistence in spite of adequate antibody titers. These HBsAg escape mutants harbor single or double point mutations that may significantly alter the immunological characteristics of HBsAg. Most escape mutations that influence HBsAg recognition by anti-HBs antibodies are located in the second ‘a’ determinant loop. Notably, HBsAg with an arginine replacement for glycine at amino acid 145 is considered the quintessential immune escape mutant because it has been isolated consistently in clinical samples of HBIg-treated individuals and vaccinated infants of chronically infected mothers. Direct binding studies with monoclonal antibodies demonstrated a more dramatic impact of this mutation on anti-HBs antibody recognition, compared with other point mutations in this antigenic domain. The clinical and epidemiological significance of these emerging HBsAg mutants will be a matter of research for years to come, especially as data available so far document that these mutants are viable and infectious strains. Strategies for vaccination programs and posttransplantation prophylaxis of recurrent hepatitis need to be developed that may prevent immune escape mutant HBV from spreading and to prevent these strains from becoming dominant during the next decennia.

Serological and molecular epidemiological outcomes after two decades of universal infant hepatitis B virus (HBV) vaccination in Nunavut, Canada

“…The vaccine utilizes a genotype A2 sequence, which has been shown to be protective across all genotypes, as the majority of protective antibodies are produced against HBsAg within the very conserved 'a' determinant region. It has been reported that mutations within the 'a' determinant lead to immune escape mutants and breakthrough infections [85].…”

Resilience and mental health

“…Although terminology relating to somatic disorders, such as trauma and stress, are now commonly used in mental health research and clinical practice, other positive concepts such as immune prophylaxis (Cooreman, Leroux-Roels, & Paulij, 2001) and hygiene (Yazdanbakhsh, Kremsner, & van Ree, 2002), although also potentially meaningful in relation to mental health, have not been considered. Only recently has the possibility of an immunity model been accepted in relation to mental well-being, but in terms of resilience (Bonanno, 2004), meaning more than simply the absence of disorder.…”

PROPORTION OF HBsAg AND HBeAg POSITIVE IN MATERNAL PATIENTS AND THEIR HBsAg POSITIVES BABIES WITH IMMUNOPROPHYLAXIS OF HBV IMMUNIZATION IN Dr. SOETOMO GENERAL HOSPITAL, SURABAYA

“…Hepatitis B surface antigen (HBsAg) with arginine replacement for glycine at amino acid 145 is the most common escape mutant HBsAg found in several clinical samples. 19 All infants who fail to respond to immunophrophylaxis were born from HBeAg positive mothers who had HBV DNA levels ≥6 log 10 copy/mL. The existence of HBV DNA in cord blood also reflects the failure to respond passive and active immunization.…”