Immunological Response to Parenteral Vaccination with Recombinant Hepatitis B Virus Surface Antigen Virus-Like Particles Expressing Helicobacter pylori KatA Epitopes in a Murine H. pylori Challenge Model

Abstract

Virus-like particles (VLPs) based on the small envelope protein of hepatitis B virus (HBsAg-S) are immunogenic at the B-and T-cell level. In this study, we inserted overlapping sequences encoding the carboxy terminus of the Helicobacter pylori katA gene product into HBsAg-S. The HBsAg-S-KatA fusion proteins were able to assemble into secretion-competent VLPs (VLP-KatA). The VLP-KatA proteins were able to induce KatA-specific antibodies in immunized mice. The mean total IgG antibody titers 41 days post-primary immunization with VLP-KatA (2.3 ؋ 10 3 ) were significantly greater (P < 0.05) than those observed for vaccination with VLP alone (5.2 ؋ 10 2 ). Measurement of IgG isotypes revealed responses to both IgG1 and IgG2a (mean titers, 9.0 ؋ 10 4 and 2.6 ؋ 10 4 , respectively), with the IgG2a response to vaccination with VLP-KatA being significantly higher than that for mice immunized with KatA alone (P < 0.05). Following challenge of mice with H. pylori, a significantly reduced bacterial load in the gastric mucosa was observed (P < 0.05). This is the first report describing the use of VLPs as a delivery vehicle for H. pylori antigens.

Hepatitis B Virus (HBV) Subviral Particles as Protective Vaccines and Vaccine Platforms

“…Chimeric SVPs can be constructed from viral capsid proteins, such as capsids from HBV, human papilloma virus, and Qβ phage that have been re-engineered to express foreign antigenic sequences at a high antigenic density [8,187]. Similarly, SVPs derived from the HBV envelope assemble into highly compact lipid-containing particles, and have been exploited as carrier platforms for foreign antigenic sequences by introducing N-or C-terminal extensions [188][189][190][191], N-terminal extensions in addition to substitutions of the HBsAgS N-terminal sequence [192], by replacing the HBsAgM preS2-domain [193,194], by insertions into the external loop region including replacing antigenic determinants [195][196][197][198][199][200][201], or by replacing HBsAgS-specific cytotoxic T lymphocyte (CTL) epitopes [202] ( Table 2). The insertion of a poliovirus-specific epitope with a length of 11 amino acids into the external loop region of HBsAgS allowed the expression of the chimeric, assembly and secretion competent HBsPolioAg proteins in a mouse cell line [201,203].…”

“…The induction of anti-HBs antibodies is compromised, possibly because the high content of the CS-polypeptide blocks access to the HBsAg external loop region, which contains the antigenic "a"-determinant [208]. [192,209] HBsAgS-NANP repeats Malaria Insertion HEK293F cell line M-HBsAg-N4, -N9 [195] HBsAgS-HCV env epitopes Hepatitis C virus Insertion HEK293T cell line [196,198] HBsAgS-catalase epitope Helicobacter pylori Insertion HuH-7 VLP-KatA [197] HBsAgS-VP1 capsid epitope Poliovirus Insertion Mouse L cells HBsPolioAg [201,203] HBsAgS-matrix CTL epitope Influenza A virus Insertion/Substitution HEK293T cell line [202] Polyepitope-HBsAgS; HIV Substitution preS2 sequence SW480 cells [193] CS-circumsporozoite polypeptide; DENV-EDIII-Dengue virus envelope domain III; env-envelope protein; HCV-hepatitis C virus; HIV-Human immunodeficiency virus; CTL-cytotoxic T lymphocyte. VLP-virus-like particle.…”

Immunogenicity of Leishmania-derived hepatitis B small surface antigen particles exposing highly conserved E2 epitope of hepatitis C virus

“…sHBsAg tertiary structure forms a highly conserved, hydrophilic loop containing the major B-cell epitopes also known as the “a”-determinant [ 16 , 17 ]. Because of its immunogenic potential, sHBsAg was also applied as an antigen carrier to deliver foreign sequences and induce anti-foreign humoral and cellular responses [ 13 , 18 – 25 ].…”

Hepatitis B Surface Antigen S Gene is an Effective Carrier Molecule for Developing GnRH DNA Immunocastration Vaccine in Mice

“…; Kotiw et al. ). Previous studies have shown that immunization against GnRH with the multiple repeat units of GnRH was more effective than using single unit of GnRH (Oonk et al.…”

“…; Kotiw et al. ). Our laboratory previously reported that fusion plasmid encoding inhibin or somatostatin gene fused with HBsAg‐S gene could improve the fertility or promote the growth in animals (Han et al.…”