In vivo administration of CD4-specific monoclonal antibody: effect on provirus load in rhesus monkeys chronically infected with the simian immunodeficiency virus of macaques.
Since monoclonal antibodies (MAb) specific for CD4 are potent inhibitors of HIV and SIV replication in vitro, we explored their potential usefulness in vivo as an AIDS therapy. The anti-CD4 MAb 5A8 binds to domain 2 of the CD4 molecule and inhibits virus replication and virus-induced cell fusion at a postvirus binding step. Administration of this MAb to normal rhesus monkeys coats all circulating and lymph node CD4 cells and induces neither CD4 cell clearance nor measurable immunosuppression. In the present study, monkeys chronically infected with the simian immunodeficiency virus of macaques (SIVmac) had stable levels of SIVmac provirus in PBMC prior to treatment as measured by a quantitative polymerase chain reaction technique. Six infected monkeys treated with anti-CD4 MAb demonstrated a significant decrease in SIVmac provirus level after 9 days. Of these monkeys, 3 had > 800 CD4 cells/microliter and developed strong antimouse Ig responses that prevented further treatment. The remaining 3 monkeys had < 800 CD4 cell/microliter and failed to develop antimouse Ig antibody responses. When treatment was continued for 12-21 days in these monkeys, a sustained or further decrease in SIVmac provirus load occurred over the extended treatment period. Four monkeys that received a control MAb of irrelevant specificity for 9-22 days showed either no significant change or a transient increase in SIVmac provirus. Thus, the passive administration of anti-CD4 MAb may exert a specific antiviral effect in controlling immunodeficiency virus infection in vivo.
Reimann
K A
KA
Harvard Medical School, Beth Israel Hospital, Boston, Massachusetts 02215, USA.
Cate
R L
RL
Wu
Y
Y
Palmer
L
L
Olson
D
D
Waite
B C
BC
Letvin
N L
NL
Burkly
L C
LC
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D001483:Base Sequence; D015704:CD4 Antigens / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D017931:DNA Primers / Q000235:genetics; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D015658:HIV Infections / Q000628:therapy / Q000821:virology; D006801:Humans; D016219:Immunotherapy, Adoptive; D008253:Macaca mulatta; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011533:Proviruses / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000628:therapy* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D014779:Virus Replication / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D017931:DNA Primers; D004279:DNA, Viral