At least three epitopes are recognized by the human repertoire in the hepatitis B virus group a antigen inducing protection; possible consequences for seroprevention and serodiagnosis.
Many recent investigations have shown that both HBV and anti-HBs antibodies coexist in the same patient, and HBV can be found in individuals with anti-HBc antibodies in the absence of immunologically detectable HBsAg. In most cases, mutant forms of HBV affecting the region of the envelope gene coding for the group a determinant recognized by human antibodies have been found. The nature of the group a determinant was revisited with an ELISA involving dissociated, but not alkylated, envelope subunits. No antibody recognizing a continuous epitope of the major S envelope protein could be found in humans; the full activity of human anti-HBs antibodies appeared to be focused on the discontinuous group a determinant. The immunological human repertoire against the HBsAg group a determinant was analysed by competitive inhibition of three mouse monoclonal antibodies (mAbs) selected as recognizing three distinct specificities on the group a determinant. Antibodies to specificities #1 and 3 were found in 52/70 anti-HBs human sera and generally predominated over specificity #2, which was lacking in some sera. The heterogeneity of the group a determinant suggested by these data argue for the use of more than one type of anti-HBs mAb for seroprevention of recurrence after liver transplantation and HBs serodiagnosis. Provided all three types of mAbs characterized here recognize HBV variants with mutations in the a determinant and are virus-neutralizing, it may be helpful, after association of such mAbs, to use them for diagnosis and to devise new immunotherapeutic strategies to prevent emergence of HBsAg escape mutants.
Laboratoire d'Epidémiologie moléculaire des Entérovirus, Institut Pasteur, Paris, France.
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Maillard
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Pillot
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D001667:Binding, Competitive; D004797:Enzyme-Linked Immunosorbent Assay; D018985:Epitopes, B-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D006509:Hepatitis B / Q000175:diagnosis / Q000276:immunology / Q000517:prevention & control; D006510:Hepatitis B Antibodies / Q000096:biosynthesis / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000737:chemistry / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D051379:Mice; D011487:Protein Conformation; D012698:Serologic Tests; D014759:Viral Envelope Proteins / Q000276:immunology
D000911:Antibodies, Monoclonal; D018985:Epitopes, B-Lymphocyte; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D014759:Viral Envelope Proteins