Recombinant core particles of hepatitis B virus exposing foreign antigenic determinants on their surface

Abstract

Insertion of foreign oligopeptide sequences (4G50 amino acids in length) into the Pro144 position of hepatitis B core antigen (HBcAg) leads to the formation of chimeric capsids in Escherichia co/i cells. These capsids are morphologically and immunogically similar to native HBcAg, but expose the inserted oligopeptides on their outer surface and exhibit antigenic and immunogenic characteristics of the latter. As a source of model antigenic determinants, the appropriate DNA copies excised from cloned viral genes such as the pm-S region of hepatitis B virus, the transmembrane protein gp41 of human immunodeficiency virus 1 and the envelope protein gp51 of bovine leukemia virus have been used. The localization of the inserted antigenic determinants on the surface of chimeric capsids does not depend on the presence or absence of the arginine-rich, 39 amino acidlong C terminus of HBcAg.Hepatitis B core antigen; PreS region; Human immunodeficiency virus-l transmembrane protein gp41; Bovine leukemia virus envelope protein gp51; Antigenic determinant

Reverse Transcriptase- and RNA Packaging Signal-Dependent Incorporation of APOBEC3G into Hepatitis B Virus Nucleocapsids

“…Unexpectedly, we found that at higher concentrations of proteinase K, the capsid signal displayed an upshift pattern. The cause of the shift could be due to the removal of associated proteins from the exterior of the capsid or the cleavage of the C-terminal tail of the core protein, which is believed to extend out from the capsid, at least sometimes (7,45,46). Interestingly, a similar pattern was observed when HBV capsids were treated with SDS.…”

Development of a nasal vaccine for chronic hepatitis B infection that uses the ability of hepatitis B core antigen to stimulate a strong Th1 response against hepatitis B surface antigen

“…1 In vaccine studies, HBcAg is a potent immunogen even in the absence of adjuvant, and can be used as a carrier molecule for homologueous and heterologous epitopes. [2][3][4][5][6] HBsAg is the antigen used in the commercial recombinant HBV vaccine, which has been proven over the last 20 years to be a very safe and effective prophylactic vaccine against HBV infection. 7 However, there remains a need for development of more potent hepatitis B vaccines, both for use as prophylactic vaccines in poor responders to the current HBV vaccines and for use in therapeutic HBV vaccination.…”

“…27 This is related to the ability of HBcAg to act as a potent B-cell activator, enabling activated B cells to work efficiently as primary APC. 4,5 Another explanation for the strong immunogenicity of HBcAg is the presence of nucleic acids bound to the C-terminal region of the HBcAg molecule. These nucleic acids are copurified with HBcAg as a nucleoprotein from Escherichia coli .…”

The nucleocapsid of the hepatitis B virus: a remarkable immunogenic structure

“…It has been proposed that these pores are essential to allow nucleotides access to the capsid interior during the DNA synthesis and it is also relevant to the reported accessibility of the C-terminal tail to proteinases and antibodies (Machida et al, 1991;Wynne et al, 1999). When the C-terminal region is replaced by foreign inserted sequences, these insertions can be detected by special antibodies on the outside of the assembled capsids (Borisova et al, 1989).…”