Neutralizing monoclonal antibodies block human immunodeficiency virus type 1 infection of dendritic cells and transmission to T cells.
Prevention of the initial infection of mucosal dendritic cells (DC) and interruption of the subsequent transmission of HIV-1 from DC to T cells are likely to be important attributes of an effective human immunodeficiency virus type 1 (HIV-1) vaccine. While anti-HIV-1 neutralizing antibodies have been difficult to elicit by immunization, there are several human monoclonal antibodies (MAbs) that effectively neutralize virus infection of activated T cells. We investigated the ability of three well-characterized neutralizing MAbs (IgG1b12, 2F5, and 2G12) to block HIV-1 infection of human DC. DC were generated from CD14(+) blood cells or obtained from cadaveric human skin. The MAbs prevented viral entry into purified DC and the ensuing productive infection in DC/T-cell cultures. When DC were first pulsed with HIV-1, MAbs blocked the subsequent transmission to unstimulated CD3(+) T cells. Thus, neutralizing antibodies can block HIV-1 infection of DC and the cell-to-cell transmission of virus from infected DC to T cells. These data suggest that neutralizing antibodies could interrupt the initial events associated with mucosal transmission and regional spread of HIV-1.
Frankel
S S
SS
Division of Retrovirology, Walter Reed Army Institute of Research and Henry M. Jackson Foundation for the Advancement of Military Medicine, Rockville, Maryland, USA. sfrankel@hiv.hjf.org
Steinman
R M
RM
Michael
N L
NL
Kim
S R
SR
Bhardwaj
N
N
Pope
M
M
Louder
M K
MK
Ehrenberg
P K
PK
Parren
P W
PW
Burton
D R
DR
Katinger
H
H
VanCott
T C
TC
Robb
M L
ML
Birx
D L
DL
Mascola
J R
JR
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000166:cytology / Q000821:virology*; D015483:HIV Antibodies / Q000494:pharmacology*; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control / Q000635:transmission; D015497:HIV-1 / Q000276:immunology* / Q000472:pathogenicity*; D006801:Humans; D066298:In Vitro Techniques; D009092:Mucous Membrane / Q000166:cytology / Q000821:virology; D009500:Neutralization Tests; D013601:T-Lymphocytes / Q000821:virology*
D000911:Antibodies, Monoclonal; D015483:HIV Antibodies