Hepatitis B surface antigen (HBsAg), the envelope proteins of hepatitis B virus (HBV), induce protective immune response. The region comprising amino acid (aa) residues 124–147 of HBsAgis termed as the “a” determinant and harbors a cluster of epitopes targeted by neutralizing anti-HBs antibodies.A variety of aa substitutions have been identified within or around HBsAg “a” determinant. VtHBsAgs with these aa substitutions result in reduced ability to bind to anti-HBs antibodies, and subsequently lead to immune escape.