Blocking of HSV spread with either antibody directed against known HSV entry receptors or HSV glycoproteins. (A) PBMC stimulated with PHA (1 μg/ml for 2 days at 37°C) were coincubated for 2 h at 37°C with fibroblasts infected with HSV-1(F) at an MOI of 10 for 16 h in the presence of various dilutions of antibody. For anti-HVEM and anti-nectin-1, the diluted antibodies were added to the PBMC and incubated for 20 min at 37°C before coincubation with the infected fibroblasts. For anti-gB, anti-gD, and anti-gH-gL, the diluted antibodies were added to the infected fibroblasts and incubated for 20 min at 37°C before coincubation with the PBMC. After the 2-h coincubation, the T cells were removed, washed with citrate buffer and PBS, further incubated at 37°C in culture medium for 24 h, stained for CD3 and HSV antigens, and analyzed by flow cytometry. The table indicates the reactivity of the different antibodies used in the experiment. Antibody binding and the ability to block infection were confirmed by direct infection of control HEp-2 cells in the presence of antibody and ranged from ∼90% to ∼40% inhibition of infection relative to cells in the absence of antibody (R8 > SS10 > R137 ≈ CK41 ≈ HVEM) (data not shown). (B) PBMC stimulated with PHA as described in panel A were coincubated for 2 h at 37°C with fibroblasts infected with HSV-1(F) at an MOI of 10 for 16 h in the presence of MAb dilutions directed against different gD epitopes. The diluted antibodies were added to the infected fibroblasts and incubated for 20 min at 37°C before coincubation with the PBMC. After the 2-h coincubation, the T cells were removed, washed with citrate buffer and PBS, further incubated at 37°C in culture medium for 24 h, stained for CD3 and HSV antigens, and analyzed by flow cytometry. The table indicates the ability of the different MAbs to block gD binding to HVEM and/or nectin-1. Antibody binding and the ability to block infection were confirmed by performing direct infection of control HEp-2 cells in the presence of antibody and ranged from ∼90% to ∼20% inhibition of infection (DL11 > 1D3 ≈ HD1 ≈ DL6) (data not shown). Both panels show results from duplicate wells from one representative of two independent experiments.