In vitro neutralization of hepatitis B virus by monoclonal antibodies against the viral surface antigen

Ryu, Chun Jeih; Gripon, Philippe; Park, Heung Rok; Park, Sung Sup; Kim, Youn Kyu; Guguen‐Guillouzo, Christiane; Yoo, Ook Joon; Hong, Hyo Jeong

doi:10.1002/(sici)1096-9071(199706)52:2<226::aid-jmv18>3.0.co;2-i

Cited by 41 publications

(25 citation statements)

References 41 publications

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“…The "a" determinant of HBsAg induces HBV-neutralizing antibodies regardless of the virus subtype (40), and they provide up to 2,000-fold-higher specific activities than the polyclonal antibodies induced by whole HBV (41). Immunization of BALB/c mice with the purified NvC-aD resulted in the production of antibodies specifically against both the "a" determinant peptide and the "a" determinant present in the plasma-purified HBsAg.…”

Section: Discussionmentioning

confidence: 95%

Induction of Humoral and Cell-Mediated Immune Responses by Hepatitis B Virus Epitope Displayed on the Virus-Like Particles of Prawn Nodavirus

Yong

Yeap

Goh

et al. 2015

Appl Environ Microbiol

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Hepatitis B virus (HBV) is a deadly pathogen that has killed countless people worldwide. Saccharomyces cerevisiae-derived HBV vaccines based upon hepatitis B surface antigen (HBsAg) is highly effective. However, the emergence of vaccine escape mutants due to mutations on the HBsAg and polymerase genes has produced a continuous need for the development of new HBV vaccines. In this study, the "a" determinant within HBsAg was displayed on the recombinant capsid protein of Macrobrachium rosenbergii nodavirus (MrNV), which can be purified easily in a single step through immobilized metal affinity chromatography (IMAC). The purified protein self-assembled into virus-like particles (VLPs) when observed under a transmission electron microscope (TEM). Immunization of BALB/c mice with this chimeric protein induced specific antibodies against the "a" determinant. In addition, it induced significantly more natural killer and cytotoxic T cells, as well as an increase in interferon gamma (IFN-␥) secretion, which are vital for virus clearance. Collectively, these findings demonstrated that the MrNV capsid protein is a potential carrier for the HBV "a" determinant, which can be further extended to display other foreign epitopes. This paper is the first to report the application of MrNV VLPs as a novel platform to display foreign epitopes. Hepatitis B virus (HBV) is a partially double-stranded DNA virus that belongs to the family Hepadnaviridae. It is known to be the major cause of liver-associated diseases, including liver cirrhosis and hepatocellular carcinoma. Approximately 2 billion people worldwide have been infected by HBV, among which about 350 million chronically infected people serve as a reservoir for the virus (1, 2). To date, there is no effective treatment for HBV infection despite intensive studies on antiviral drugs. Thus, preventive measures, including immunization with HBV vaccine, remain necessary.HBV surface antigens (HBsAg) purified from the sera of infected patients have been used for immunization against HBV infection since 1981. The full-length HBsAg gene has three different start codons and a common stop codon and encodes HBsAg of different lengths (3). The longest is the large HBsAg (L-HBsAg), followed by the middle HBsAg (M-HBsAg), and the smallest is the small HBsAg (S-HBsAg). L-HBsAg is composed of 389 or 400 amino acids (aa), depending on the virus genotypes. It contains the pre-S1 region (108 or 119 aa), followed by the pre-S2 region (55 aa) and S-HBsAg (226 aa). The N-terminal end of M-HBsAg harbors the pre-S2 region at its S-HBsAg. The S-HBsAg contains 226 aa in the absence of the pre-S1 and pre-S2 regions.The HBsAg in serum self-assemble into noninfectious 22-nm spherical or filamentous particles, along with lipid components (4), which are capable of inducing neutralizing antibodies against HBV infection. Although highly effective, the use of plasma-derived HBsAg for vaccination is limited by the production cost, as well as the possibility of contamination by other infectious pathogens present in...

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Section: Discussionmentioning

confidence: 95%

Induction of Humoral and Cell-Mediated Immune Responses by Hepatitis B Virus Epitope Displayed on the Virus-Like Particles of Prawn Nodavirus

Yong

Yeap

Goh

et al. 2015

Appl Environ Microbiol

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“…Such a concept is even more attractive, since in the course of a natural infection, the successful eliciting of a massive anti-preS antibody response is in most cases the decision point for a successful viral clearance. Genetically engineered humanized anti-preS antibodies might be a solution for the production of such prophylactic reagents, which are also under development by several research groups (20,33) either in the form of mono-or polyclonal antibodies (30).…”

Section: Resultsmentioning

confidence: 99%

Determination of the Protective Effects of Neutralizing Anti‐Hepatitis B Virus (HBV) Immunoglobulins by Epitope Mapping with Recombinant HBV Surface‐Antigen Proteins

Park

Cho

Lee

et al. 2000

Microbiology and Immunology

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Anti-hepatitis B virus (HBV) surface-antigen immunoglobulins prepared from human sera are clinical reagents which have been approved for prophylactic treatment in HBV-exposed persons. The passive immunoprophylaxis with immunoglobulins is meant to cross-link viral particles, which are then further cleared by the host's own immune system. While antibodies specific for both anti-S-and anti-preS proteins have been proved to serve as effective anti-viral agents, so far the fine antigen specificity of clinical immunoglobulin preparations has not been determined. Using recombinant proteins covering the hepatitis B surface antigen, in the present study, the specificity of a commercially available immunoglobulin preparation was determined and immunodominant epitopes were mapped. Here, it is shown that the major reactivity of anti-HBV immunoglobulins is directed against the S-protein, and that no reactivity to the preS2 but a weak binding activity to the preS1 region was detectable. The antigen reactivity within the preS1 region was biased to the C-terminal region, which indicates the presence of a putative B-cell epitope. The evaluation of the antigen specificity and determination of novel protective epitopes will provide valuable information for the further development and improvement of prophylactic HBV immunoglobulins.

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“…Interestingly, this sequence constitutes a highly immunogenic pre-S epitope that is present on either complete hepadnaviral particles (28) or recombinant pre-S polypeptides (unpublished data). Antibodies directed against those antigens neutralize infection (8,26; unpublished data), possibly by preventing virus binding to its cellular receptor. In contrast, HBVpreS/2-48 myr was added just 4 h after removal of the infectious inoculum and was then left on the cells for an additional 16 h. Alternatively, HBVpreS/2-48 myr was incubated with HepaRG cells at the indicated concentrations (incubation time, 16 h).…”

Section: Discussionmentioning

confidence: 99%

Efficient Inhibition of Hepatitis B Virus Infection by Acylated Peptides Derived from the Large Viral Surface Protein

Gripon

Cannie

Urban

2005

J Virol

Self Cite

312

292

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The lack of an appropriate in vitro infection system for the major human pathogen hepatitis B virus (HBV) has prevented a molecular understanding of the early infection events of HBV. We used the novel HBVinfectible cell line HepaRG and primary human hepatocytes to investigate the interference of infection by HBV envelope protein-derived peptides. We found that a peptide consisting of the authentically myristoylated N-terminal 47 amino acids of the pre-S1 domain of the large viral envelope protein (L protein) specifically prevented HBV infection, with a 50% inhibitory concentration (IC 50 ) of 8 nM. The replacement of myristic acid with other hydrophobic moieties resulted in changes in the inhibitory activity, most notably by a decrease in the IC 50 to picomolar concentrations for longer unbranched fatty acids. The obstruction of HepaRG cell susceptibility to HBV infection after short preincubation times with the peptides suggested that the peptides efficiently target and inactivate a receptor at the hepatocyte surface. Our data both shed light on the molecular mechanism of HBV entry into hepatocytes and provide a basis for the development of potent hepadnaviral entry inhibitors as a novel therapeutic concept for the treatment of hepatitis 〉.The human hepatitis B virus (HBV) causes acute and chronic liver infections in humans. Owing to the propensity of HBV to establish persistent infections, about 400 million people worldwide have an Ϸ100-fold higher risk of developing liver cirrhosis and hepatocellular carcinoma than uninfected people. As a consequence, about 1 million people die every year from HBV-related end-stage liver failure (27). Thus, regardless of the availability of a vaccine and the possibility to therapeutically interfere with genome replication in already infected cells, there is a vital need for the development of agents that protect healthy hepatocytes from infection (e.g., by interference with virus entry) and hence bear the potential to be curative (13).HBV belongs to the family Hepadnaviridae, which includes small enveloped partially double-stranded DNA viruses infecting primates, rodents, and birds (7). Hepadnaviruses possess remarkable species specificities and preferentially target parenchymal liver cells of their respective natural hosts. Experimental in vitro HBV infections have so far only been successful in highly differentiated primary hepatocytes of humans (PHH) (9) and, surprisingly, Tupaia belangeri (8) or in the recently described HepaRG cell line (11). In vivo studies have been restricted to chimpanzees or, as alternatives of unclear relevance, the animal models Pekin ducks (19) and woodchucks (30), using the corresponding duck HBV (DHBV) and woodchuck HBV, respectively. Since the delivery (e.g., by transfection) of hepadnaviral genomes into nonsusceptible cell lines of diverse origins results in the replication, assembly, and secretion of infectious particles (1, 5), it has been assumed that the described limitations are related to some early infection events (receptor recogniti...

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In vitro neutralization of hepatitis B virus by monoclonal antibodies against the viral surface antigen

Cited by 41 publications

References 41 publications

Induction of Humoral and Cell-Mediated Immune Responses by Hepatitis B Virus Epitope Displayed on the Virus-Like Particles of Prawn Nodavirus

Induction of Humoral and Cell-Mediated Immune Responses by Hepatitis B Virus Epitope Displayed on the Virus-Like Particles of Prawn Nodavirus

Determination of the Protective Effects of Neutralizing Anti‐Hepatitis B Virus (HBV) Immunoglobulins by Epitope Mapping with Recombinant HBV Surface‐Antigen Proteins

Efficient Inhibition of Hepatitis B Virus Infection by Acylated Peptides Derived from the Large Viral Surface Protein

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