Depletion in antibodies targeted to the HR2 region of HIV-1 glycoprotein gp41 in sera of HIV-1-seropositive patients treated with T20.
The anti-HIV drug T20 is a synthetic peptide derived from the HR2 region of HIV-1 gp41. T20 contains the sequence ELDKWA, which binds the broadly neutralizing antibody 2F5. Using plates coated with T20 or with synthetic peptides and recombinant proteins representing gp120 or gp41 domains, this study investigated by enzyme-linked immunosorbent assay the levels of antibodies directed to the gp160 molecule in patients treated with T20. Analysis of sera obtained before and after administration of T20 indicated that the levels of antibodies directed to T20, to MBP44, a maltose binding protein representing the HR2 region, and to 4765, a synthetic peptide containing the sequence ELDKWA, fell following administration of T20, while the levels of antibodies directed to other regions of gp41 ectodomain and to gp120 remained stable. The decline observed was independent of the viral load and of the total IgG concentration. Follow-up studies with sera obtained from HIV-1-seropositive patients naive to T20 indicated no decline in the level of antibodies directed to HR2 and other regions of gp160. Analysis of sera obtained from a patient after 2 months of T20 treatment interruption showed a level of antibodies to the HR2 region similar to that measured before administration of T20. The addition of increasing amounts of T20 to sera from T20-naive patients decreased the level of serum antibodies against peptide 4765, T20, and MBP44. The observation of antibody depletion by T20 suggests that anti-gp41 antibodies may interfere with T20 treatment by forming T20-antibody complexes.
Vincent
Nadine
N
Groupe Immunité des Muqueuses et Agents Pathogènes, Faculty of Medicine of Saint-Etienne, France.
Tardy
Jean-Claude
JC
Livrozet
Jean-Michel
JM
Lucht
Frédéric
F
Frésard
Anne
A
Genin
Christian
C
Malvoisin
Etienne
E
D000328:Adult; D000595:Amino Acid Sequence; D000936:Antigen-Antibody Complex; D023241:Antiretroviral Therapy, Highly Active; D002352:Carrier Proteins / Q000276:immunology; D000077560:Enfuvirtide; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015483:HIV Antibodies / Q000097:blood*; D015488:HIV Antigens / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015700:HIV Envelope Protein gp41 / Q000276:immunology* / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D058619:Maltose-Binding Proteins; D008875:Middle Aged; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology / Q000627:therapeutic use*; D019562:Viral Load
D000936:Antigen-Antibody Complex; D002352:Carrier Proteins; D015483:HIV Antibodies; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D007074:Immunoglobulin G; D058619:Maltose-Binding Proteins; D009842:Oligopeptides; D010446:Peptide Fragments; D000077560:Enfuvirtide