HTLV- 1 infection in hu- PBMC- NOG- spl mice was completely inhibited by neutralizing, but not non- neutralizing, antibodies. In vivo transmission of HTLV-1 and protective efficacy of various monoclonal antibodies was evaluated using quantitative real-time PCR analysis of HTLV-1 proviral DNA. Genomic DNA was extracted from the human lymphocytes recovered from hu-PBMC-NOG-spl mice. A. All of the mice immunized with neutralizing mAbs against Env (clone LAT-27) were completely protected against HTLV-1 infection, whereas non-neutralizing mAbs against Env (clone LAT-25), anti-Gag (clone GIN-7), anti-HCV (clone MO-8), or anti-OX40 mAb (clone B-7B5) did not protect against infection. The mice immunized with human immunoglobulin isolated from HAM/TSP patients (HAM-IgG) were also protected against HTLV-1 infection, whereas human IgG isolated from normal uninfected controls (NC-IgG) did not protect against infection. Results are shown as mean × SE. To test for significant differences among the different groups, one-way analysis of variance was performed, followed by Scheffe’s multiple comparisons test. The lower limit of detection was one copy of HTLV-1 tax per 104 PBMCs. B. Flow cytometric studies indicated that the human lymphocytes recovered from mouse spleens immunized with anti-Env neutralizing mAbs or HAM-IgG express only a trace amount of Tax protein after short-term (16 h) cultivation ex vivo, which may be a background false-positive staining artifact. In contrast, a significant amount of Tax protein was expressed in human lymphocytes recovered from non-immunized mouse spleens (PBS-injected) or mouse spleens immunized with NC-IgG. The numbers represent the percentage of the cell population within the HLA-class I-positive/CD4-positive gate.