Synergistic neutralization of a chimeric SIV/HIV type 1 virus with combinations of human anti-HIV type 1 envelope monoclonal antibodies or hyperimmune globulins.
A panel of 14 human IgG monoclonal antibodies (MAbs) specific for envelope antigens of the human immunodeficiency virus type 1 (HIV-1), 2 high-titer human anti-HIV-1 immunoglobulin (HIVIG) preparations, and 15 combinations of MAbs or MAb/HIVIG were tested for their ability to neutralize infection of cultured human T cells (MT-2) with a chimeric simian immunodeficiency virus (SHIV-vpu+), which expressed HIV-1 IIIB envelope antigens. Eleven MAbs and both HIVIGs were neutralizing. When used alone, the anti-CD4-binding site MAb b12, the anti-gp41 MAb 2F5, and the anti-gp120 MAb 2G12 were the most potent. When combination regimens involving two MAbs targeting different epitopes were tested, synergy was seen in all paired MAbs, except for one combination that revealed additive effects. The lowest effective antibody concentration for 50% viral neutralization (EC50) and EC90 were achieved with combinations of MAbs b12, 2F5, 2G12, and the anti-V3 MAb 694/98D. Depending on the combination regimen, the concentration of MAbs required to reach 90% virus neutralization was reduced approximately 2- to 25-fold as compared to the dose requirement of individual MAbs to produce the same effect. Synergy of the combination regimens implies that combinations of antibodies may have a role in passive immunoprophylaxis against HIV-1. The ability of SHIV to replicate in rhesus macaques will allow us to test such approaches in vivo.
Li
A
A
Laboratory of Viral Pathogenesis, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Baba
T W
TW
Sodroski
J
J
Zolla-Pazner
S
S
Gorny
M K
MK
Robinson
J
J
Posner
M R
MR
Katinger
H
H
Barbas
C F
CF
Burton
D R
DR
Chou
T C
TC
Ruprecht
R M
RM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology*; D002478:Cells, Cultured; D002678:Chimera / Q000187:drug effects / Q000235:genetics*; D004357:Drug Synergism; D015483:HIV Antibodies / Q000276:immunology* / Q000302:isolation & purification / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D054298:Human Immunodeficiency Virus Proteins; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology* / Q000494:pharmacology; D008253:Macaca mulatta; D009500:Neutralization Tests; D015302:Simian Immunodeficiency Virus / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology; D054334:Viral Regulatory and Accessory Proteins / Q000187:drug effects / Q000276:immunology; D000086082:Viroporin Proteins
D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; D015483:HIV Antibodies; D054298:Human Immunodeficiency Virus Proteins; D007136:Immunoglobulins; D014759:Viral Envelope Proteins; D054334:Viral Regulatory and Accessory Proteins; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins