Neutralization of primary human immunodeficiency virus type 1 isolates by the broadly reactive anti-V3 monoclonal antibody, 447-52D.
Human monoclonal antibody 447-52D binds to the V3 determinant of the human immunodeficiency virus type 1 (HIV-1) gp120 external glycoprotein. Its binding requires the expression of the GPxR sequence at the center of the V3 domain. HIV-1 variants that are adapted to replication in T-lymphoid cell lines and express this sequence motif are efficiently neutralized by the antibody (M. K. Gorny, A. J. Conley, S. Karwowska, A. Buchbinder, J.-Y. Xu, E. A. Emini, S. Koenig, and S. Zolla-Pazner, J. Virol. 66:7538-7542, 1992). In the present study, the antiviral activity of 447-52D was further defined with regard to its ability to mediate neutralization of primary HIV-1 clinical isolates. Again, the antibody was found to potently neutralize those isolates that expressed the binding sequence. We confirmed that this determinant is commonly expressed by virus isolates belonging to the subtype (clade) B sequence classification. As such, 447-52D may be useful for prophylactic and immunotherapeutic intervention. In addition, the study demonstrated that neutralization of primary HIV-1 isolates is possible if mediated by an appropriate antibody.
Conley
A J
AJ
Department of Antiviral Research, Merck Research Laboratories, West Point, Pennsylvania 19486.
Gorny
M K
MK
Kessler
J A
JA
Boots
L J
LJ
Ossorio-Castro
M
M
Koenig
S
S
Lineberger
D W
DW
Emini
E A
EA
Williams
C
C
Zolla-Pazner
S
S
D016915:AIDS Vaccines / Q000276:immunology; D000163:Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001483:Base Sequence; D002478:Cells, Cultured; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D009500:Neutralization Tests
D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D015699:HIV Envelope Protein gp120