Are International Units of Anti-HBs Antibodies Always Indicative of Hepatitis B Virus Neutralizing Activity?

Objective: Anti-HBs antibodies are elicited upon hepatitis B vaccination, and concentrations above 10 mIU/mL are considered protective. Our aim was to assess the relationship between IU/mL of anti-HBs and neutralization activity. Methods: Immunoglobulins G (IgGs) were purified from individuals who received a serum-derived vaccine (Group 1), a recombinant vaccine, Genevac-B or Engerix-B (Group 2), or who recovered from acute infection (Group 3). IgGs were tested for anti-HBs, anti-preS1, and anti-preS2 antibodies and for their neutralizing activity in an in vitro infection assay. Results: Anti-HBs IUs/mL value did not strictly correlate with neutralization activity. The Group 1 antibodies demonstrated a greater neutralizing activity than those of Group 2. Anti-preS1 antibodies were detected in Groups 1 and 3, and anti-preS2 in Group 1 and Group 2/Genhevac-B, but the contribution of anti-preS antibodies to neutralization could not be demonstrated. Virions bearing immune escape HBsAg variants were less susceptible to neutralization than wild-type virions. Conclusion. The level of anti-HBs antibodies in IUs is not sufficient to assess neutralizing activity. Consequently, (i) an in vitro neutralization assay should be included in the quality control procedures of antibody preparations intended for HB prophylaxis or immunotherapy, and (ii) a greater emphasis should be placed on ensuring that vaccine genotype/subtype matches with that of the circulating HBV.