Immunological and virological interactions in patients receiving passive immunotherapy with HIV-1 neutralizing monoclonal antibodies.
Mouse monoclonal antibodies with high human immunodeficiency virus type 1 (HIV-1) neutralizing titers were used for passive immunotherapy of eleven late-state HIV-infected patients. In five patients the serum level of the core protein p24 decreased, while in five cases it remained unchanged. The level of viral RNA in plasma as measured by quantitative polymerase chain reaction (PCR) decreased in four cases, was stable in another four, and increased in three cases. An anti-mouse (HAMA) response developed in eight patients and anti-idiotypic antibodies appeared in six. Immune complexes that formed in patient sera during the treatment were shown to contain mostly envelope glycoprotein gp120 which decreased in nine of the eleven treated patients toward the end of treatment. Antibodies inhibiting gp120 binding to CD4 became detectable or increased in six patients during immunotherapy. Serology of the HIV-1 V3 region was studied for both the HIV-1 IIIB and MN strains with no or very small changes in titer or avidity after treatment. No change in neutralizing titers to strain HTLVIIIB was observed in serum samples collected before and after treatment was terminated. In nine of the eleven patients stimulation of the T lymphocytes to proliferate in vitro when activated by phytohemagglutinin (PHA) was shown to be increased compared to before treatment. Increased T-cell proliferation was also noted with several antigens such as HIV-1 recombinant antigens, cytomegalovirus (CMV), tetanus toxoid (TT), and purified protein derivate of mycobacterium tuberculosis (PPD). These findings indicate a decreased total gp120 content in serum, permitting better T-cell activation.
Hinkula
J
J
Department of Virology, National Bacteriological Laboratory, Stockholm, Sweden.
Bratt
G
G
Gilljam
G
G
Nordlund
S
S
Broliden
P A
PA
Holmberg
V
V
Olausson-Hansson
E
E
Albert
J
J
Sandström
E
E
Wahren
B
B
D000328:Adult; D000595:Amino Acid Sequence; D000888:Antibodies, Anti-Idiotypic / Q000097:blood; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity; D000936:Antigen-Antibody Complex / Q000097:blood; D016516:CD4-CD8 Ratio; D005260:Female; D005500:Follow-Up Studies; D015483:HIV Antibodies / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use*; D016655:HIV Core Protein p24 / Q000097:blood; D015699:HIV Envelope Protein gp120 / Q000097:blood / Q000737:chemistry; D015658:HIV Infections / Q000276:immunology / Q000382:microbiology / Q000628:therapy*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D006207:Half-Life; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D016219:Immunotherapy, Adoptive; D007963:Leukocytes, Mononuclear / Q000382:microbiology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000097:blood; D013601:T-Lymphocytes / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D015483:HIV Antibodies; D016655:HIV Core Protein p24; D015699:HIV Envelope Protein gp120; D007074:Immunoglobulin G; D012367:RNA, Viral