Targeted destruction of the polymerized human serum albumin binding site within the preS2 region of the HBV surface antigen while retaining full immunogenicity for this epitope.
The 55-amino acid (a.a.) preS2 region of the hepatitis B virus (HBV) envelope protein is highly immunogenic, and antibodies against this epitope confer seroprotection against HBV infections. Accordingly, various experimental and clinical studies for developing and evaluating HBV vaccines that include this particular epitope have been reported. However, a pitfall in using preS2 epitopes as part of a vaccinating antigen is that polymerized human serum albumin (pHSA), which is a normal constituent of the human serum, binds to and makes complexes with this particular region. Consequently, it is most likely that the antigen epitope is masked by serum pHSA and subsequently not detected by the immune system. To overcome these limitations, a novel single a.a substitute of the preS2 region was designed that corresponds to a tyrosine to serine exchange at position 140 of preS2. Competitive enzyme-linked immunosorbent assay showed that this substitution completely abolishes pHSA-binding activities in the mutated preS2 peptide, and CD spectra analysis revealed that this property might have been induced by slight conformational changes in its secondary structure. Nevertheless, the original B-cell epitope was still preserved in the mutated preS2 as determined by experimental immunization in mice. In this regard, the preS2(120-145/Y140S) sequence may be an HBV vaccine where epitopes, with intrinsic properties have been deleted without affecting the immunogenicity of the epitope itself. It is expected that the inclusion of this point mutated preS2 epitope will improve the efficacy of conventional preS2-containing HBV vaccines.
Park
J-H
JH
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Lee
M-K
MK
Kim
H-S
HS
Kim
K L
KL
Cho
E-W
EW
D000918:Antibody Specificity; D001667:Binding, Competitive; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D006514:Hepatitis B Surface Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D011498:Protein Precursors / Q000737:chemistry / Q000276:immunology*; D012709:Serum Albumin / Q000378:metabolism*
D006514:Hepatitis B Surface Antigens; D016056:Immunodominant Epitopes; D011498:Protein Precursors; D012709:Serum Albumin; C050807:presurface protein 2, hepatitis B surface antigen