Enhanced Immunogenicity of the Pre-S Region of Hepatitis B Surface Antigen

Abstract

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.

Secretion of Particles of Hepatitis B Surface Antigen from Insect Cells Using a Baculovirus Vector

“…It has been claimed that the HBV pre-S2 region (Milich et al, 1985;Valenzuela et al, 1985) enhances the immunogenicity of the HBsAg. A recombinant baculovirus (AcNPV-PsSYK27) has therefore been constructed containing the coding region of the pre-S2 region (55 amino acids) as well as the HBsAg gene.…”

Vaccine engineering: enhancement of immunogenicity of synthetic peptide vaccines related to hepatitis in chemically defined models consisting of T- and B-cell epitopes.

“…Thus, our results indicate that the pre-S(2) region of the HBsAg overcame the nonresponsiveness of B-cell epitopes of the S region and may serve as a T-helper cell epitope. Enhanced immunogenicity of the S region by preimmunization with pre-S protein has been shown by Milich et al (17,18) in inbred strains of mice. They show that preimmunization with pre-S protein of mice nonresponsive to S protein results in an enhanced response to S protein after reimmunization with HBsAg containing both proteins.…”

Stable Expression of the Hepatitis B Virus Surface Antigen Containing Pre-S2 Protein in Mouse Cells Using a Bovine Papillomavirus Vector

“…The majority of such cell constructs use recombinants containing a part of the HBV genome coding for the HBsAg only. Since the pre-S2 region may protect from HBV infection in chimpanzees (Itoh et al, 1986), and have enhanced immunogenicity in animals (Milich et al, 1985; et al., 1985), the inclusion of pre-S2 protein seems preferable. Electrophoretic and pHSA binding analyses showed that the pre-S2 protein was indeed included in the HBsAg particles released from MS128 cells.…”

“…The other, called large S (P39/GP42), contains an extra 108 amino acids (pre-S1) at the amino terminus of middle S. Pre-S proteins are thought to be involved in virus attachment to hepatocytes (Machida et al, 1983;Neurath et aL, 1986) and in enhanced immunogenicity (Milich et al, 1985;Neurath et al, 1985). Therefore, much attention has been focused upon the role of pre-S proteins in HBV infection.…”