Characterization of the reactivity pattern of murine monoclonal antibodies against wild‐type hepatitis B surface antigen to g145r and other naturally occurring “a” loop escape mutations

Characterization of the reactivity pattern of murine monoclonal antibodies against wild‐type hepatitis B surface antigen to g145r and other naturally occurring “a” loop escape mutations

The hepatitis B surface antigen (HBsAg) “a” domain harbors major B‐cell epitopes. Viruses with mutations in this region emerge after vaccination or during hepatitis B immune globulin (HBIg) prophylaxis. A strain with G145R replacement has been almost invariably isolated as a major escape mutant. We...

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Bibliographic Details
Published in:Hepatology (Baltimore, Md.) Vol. 30; no. 5; pp. 1287 - 1292
Main Authors: Cooreman, Michel P., van Roosmalen, Mark H., te Morsche, René, Sünnen, Cécile M. G., Schoondermark‐van de Ven, Esther M. E., Jansen, Jan B. M. J., Tytgat, Guido N. J., de Wit, Pauline L. M., Paulij, Wilma P.
Format: Journal Article
Language:English
Published: Philadelphia, PA W.B. Saunders 01-11-1999
Wiley
Subjects:
Amino Acid Substitution
Animals
Antibodies, Monoclonal - immunology
Biological and medical sciences
COS Cells
Digestive system
Epitopes - immunology
Hepatitis B Antibodies - immunology
Hepatitis B Surface Antigens - chemistry
Hepatitis B Surface Antigens - genetics
Hepatitis B Surface Antigens - immunology
Hepatitis B virus - genetics
Hepatitis B, Chronic - immunology
Humans
Investigative techniques, diagnostic techniques (general aspects)
Medical sciences
Mice
Mutagenesis, Site-Directed
Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques
Point Mutation
Recombinant Proteins - chemistry
Recombinant Proteins - immunology
Sheep
Transfection
Immunopathology
Rodentia
Orthohepadnavirus
Hepatic disease
Monoclonal antibody
Gene expression
Experimental study
Strain
Infection
Virus
Antigen
Characterization
Viral hepatitis B
Vertebrata
Chronic
Mammalia
Hepadnaviridae
Viral disease
Animal
Muridae
Digestive diseases
Mutation
Hepatitis B virus
Immunofluorescence
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Description
Summary:The hepatitis B surface antigen (HBsAg) “a” domain harbors major B‐cell epitopes. Viruses with mutations in this region emerge after vaccination or during hepatitis B immune globulin (HBIg) prophylaxis. A strain with G145R replacement has been almost invariably isolated as a major escape mutant. We investigated mutant antigen‐antibody interactions with direct binding assays. G145R and 16 other naturally occurring recombinant HBsAg mutants were expressed in mammalian Cos‐1 cells. The reactivity of a panel of 28 murine anti‐hepatitis B surface antigen (anti‐HBs) monoclonal antibodies to mutant antigens was measured with enzyme immunoassay and expressed as percentage compared with the wild‐type (wt) HBsAg signal for each antibody. All point‐mutated proteins displayed diffuse intracellular immunofluorescent labeling corresponding to a secretory pathway. Monoclonal antibodies (mAbs) were classified according to different binding patterns. The effect of mutations on antibody binding differs depending on the amino acid involved and on the location within the “a” loop. As expected, most antibodies had absent or negligible binding (<40%), notably with residue 145 replacements. However, we identified antibodies that reacted with conformational epitopes but nevertheless had adequate reactivity (>40%) with all mutant antigens, including G145R. The effect of G145R was more pronounced than that of G145A. A subgroup of antibodies had substantially increased recognition (>120%) of antigens with mutations in the first loop. We demonstrated that antibodies can be selected or combined that react with all mutants investigated, including G145R. These data offer perspectives for improving anti‐HBs–based protection against hepatitis B.
ISSN:0270-9139
1527-3350
DOI:10.1002/hep.510300508