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.
Maillard
P
P
Laboratoire d'Epidémiologie moléculaire des Entérovirus, Institut Pasteur, Paris, France.
Pillot
J
J
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