Enhanced immunogenicity of the pre-S region of hepatitis B surface antigen.
The 55 codons upstream of the gene sequence encoding the hepatitis B surface antigen (HBsAg) are called the pre-S(2) region. It has been proposed that polypeptides of high molecular weight that contain the pre-S(2) region should be included in future hepatitis B virus (HBV) vaccines. The pre-S(2) region and the S gene product [25 kilodalton (kD)] together compose a polypeptide of high molecular weight (33 kD). As an initial attempt to determine the relevance of the 33-kD polypeptide to development of an HBV vaccine, the murine immune response to pre-S(2)-encoded determinants as compared to S-encoded determinants on the same polypeptide was examined. The results indicate (i) the pre-S(2) region is significantly more immunogenic than the S region of HBsAg, (ii) the 26 amino acid residues at the NH2-terminus of the 33-kD polypeptide represent a dominant antibody binding site on the pre-S(2) region, (iii) the immune response to the pre-S(2) region is regulated by H-2-linked genes distinct from those that regulate the response to the S region, and (iv) immunization of an S region nonresponder strain with HBV envelope particles that contain both the pre-S(2) and S regions can circumvent nonresponsiveness to the S region.
Milich
D R
DR
Thornton
G B
GB
Neurath
A R
AR
Kent
S B
SB
Michel
M L
ML
Tiollais
P
P
Chisari
F V
FV
D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D000918:Antibody Specificity; D000939:Epitopes; D005802:Genes, MHC Class II; D005814:Genes, Viral; D006510:Hepatitis B Antibodies / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008970:Molecular Weight; D011498:Protein Precursors / Q000235:genetics / Q000276:immunology; D014761:Viral Hepatitis Vaccines / Q000276:immunology*; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology
D000939:Epitopes; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D011498:Protein Precursors; D014761:Viral Hepatitis Vaccines; D014764:Viral Proteins