Virus-neutralizing Antibodies to Hepatitis B Virus: The Nature of an Immunogenic Epitope on the S Gene Peptide

Waters, Jennifer A.; Pignatelli, Massimo; Galpin, S.; Ishihara, Katsutoshi; Thomas, Heath C.

doi:10.1099/0022-1317-67-11-2467

Cited by 30 publications

(14 citation statements)

References 18 publications

(14 reference statements)

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“…Cells grown for 24 hr on glass coverslips were fixed in methanol and incubated with primary antibody at a dilution of 1:1000 and then incubated in secondary and tertiary antibodies as described (20). Mouse monoclonal antibodies against core or surface proteins (21,22) were from J. Walters (St. Mary's Hospital, London) and rabbit antipolymerase serum (20) was from M. McGarvey (St. Mary's Hospital, London).…”

Section: Methodsmentioning

confidence: 99%

Expression of the terminal protein region of hepatitis B virus inhibits cellular responses to interferons alpha and gamma and double-stranded RNA.

Foster

Ackrill

Goldin

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

144

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Constructs expressing the core, surface, X, or polymerase proteins of hepatitis B virus were transfected into human cells. In transient assays, only the polymerase inhibited the responses to interferons a and y (IFN-a and -y). Stable expression of the polymerase was achieved in the cell line 2fTGH, which carries an IFN-inducible marker gene, by growth under conditions that select for inhibition of the response to IFN-a, but the clones grew poorly. When expressed alone, the terminal protein domain of the polymerase gene inhibited the response to IFN-a and the reverse transcriptase plus RNase H domains appeared to be toxic. Clones of cells expressing terminal protein alone, selected for the loss of response to IFN-a, grew normally and had no detectable response to IFN-a, IFN-y, or double-stranded RNA. Binding of IFN-a to these cells was not impaired but did not lead to activation of the Ea subunit of the IFN-induced transcription factor E. These observations are of potential importance in relation to the pathogenesis of chronic hepatitis B virus infection and the resistance of such infection to IFN-a therapy.

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Section: Methodsmentioning

confidence: 99%

Expression of the terminal protein region of hepatitis B virus inhibits cellular responses to interferons alpha and gamma and double-stranded RNA.

Foster

Ackrill

Goldin

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

144

View full text Add to dashboard Cite

show abstract

“…It has been suggested that all of the immunogenically relevant epitopes of HBsAg reside on the p24 s -dimer unit (42). The virus neutralizing RF1 monoclonal epitope has been shown to be present on dimers but not monomers (43,44), yet interestingly the RF1 monoclonal antibody also binds effectively to a cyclic (i.e., disulfide bonded) synthetic peptide from the a determinant region of p24 s (45). This suggests that dimerization induces conformational rearrangements in the individual monomers that are prerequisites for intramolecular disulfide bridges.…”

Section: Discussionmentioning

confidence: 95%

Factors Important in the Extraction, Stability and in Vitro Assembly of the Hepatitis B Surface Antigen Derived from Recombinant Plant Systems

Smith

Keegan

Mason

et al. 2002

Biotechnology Progress

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The expression of vaccine antigens in edible plant material together with their delivery by the oral route constitutes a powerful paradigm, with the potential to dramatically reduce the cost of vaccine production and administration, in addition to improving distribution and patient compliance. These products will be subject to many of the same regulations applied to current injectable vaccines, so reliable methods to quantify antigen and ensure stability in crude plant extracts are required. As a model system the hepatitis B surface antigen (HBsAg) was expressed in soybean and tobacco cell cultures. This complex antigen consists of membrane-associated small surface antigen proteins (p24(s)), disulfide cross-linked to yield dimers and higher multimers. Although the total p24(s) extracted from plant cells was relatively unaffected by detergent concentration, the quantification of antigenically reactive product depended strongly on the ratio of detergent to cell concentration. Furthermore, 1-20% w/v sodium ascorbate improved the measured levels of monoclonal-reactive antigen 4- to 12-fold. Detergent also influenced antigen stability in cell lysates stored at 4 degrees C; under optimum conditions stability was maintained for at least 1 month, whereas excess detergent rendered the antigen susceptible to proteolytic degradation. This proteolysis could be counteracted by the addition of skim milk or its protein component, which stabilized antigenically reactive p24(s) for up to 2 months. The immunologically relevant epitopes of HBsAg are critically dependent on disulfide bonding. By altering the sodium ascorbate concentration or buffer pH the proportion of HBsAg displaying the monoclonal reactive epitopes was increased between 8- and 20-fold. In addition, under certain conditions the dimerized p24(s) could be converted to oligomeric aggregates, resembling the form of the serum-derived antigen. These simple in vitro manipulations, compatible with the goal of a minimally processed oral vaccine, may prove valuable in increasing the immunogenicity of the plant-derived antigen.

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“…This response can either lead to complete cure from the infection, and it is characterised by the production of neutralizing antibodies against HBV surface antigen (HBsAg) and adequate cytotoxic lymphocyte T-cell (CTL) responses [2][3][4], or it could result in chronic infection that leads to liver cancer (HHC), cirrhosis, or liver failure.…”

Section: Introductionmentioning

confidence: 99%

Mathematical Modeling of the Adaptive Immune Responses in the Early Stage of the HBV Infection

Allali

Meskaf

Tridane

2018

International Journal of Differential Equations

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The aim of this paper is to study the early stage of HBV infection and impact delay in the infection process on the adaptive immune response, which includes cytotoxic T-lymphocytes and antibodies. In this stage, the growth of the healthy hepatocyte cells is logistic while the growth of the infected ones is linear. To investigate the role of the treatment at this stage, we also consider two types of treatment: interferon-(IFN) and nucleoside analogues (NAs). To find the best strategy to use this treatment, an optimal control approach is developed to find the possibility of having a functional cure to HBV.

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Virus-neutralizing Antibodies to Hepatitis B Virus: The Nature of an Immunogenic Epitope on the S Gene Peptide

Cited by 30 publications

References 18 publications

Expression of the terminal protein region of hepatitis B virus inhibits cellular responses to interferons alpha and gamma and double-stranded RNA.

Expression of the terminal protein region of hepatitis B virus inhibits cellular responses to interferons alpha and gamma and double-stranded RNA.

Factors Important in the Extraction, Stability and in Vitro Assembly of the Hepatitis B Surface Antigen Derived from Recombinant Plant Systems

Mathematical Modeling of the Adaptive Immune Responses in the Early Stage of the HBV Infection

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