Evaluation of neutralizing monoclonal antibody against HTLV-1 infection in non-human primate HTLV-1 model 2871

Description Since the discovery of HTLV-1 over 4 decades ago, no effective vaccines or drugs have been developed to inhibit the infection and the pathogenesis progression. We have established a cynomolgus macaque (CM) model of HTLV-1 infection, which is believed to be essential for revealing the mechanisms of the progressive status and for the development of prevention procedures by direct intravenous inoculation of ATL-040 cells, which are HTLV-1-producing cells derived from ATL patients. This HTLV-1 CM model maintained chronic infection over a long period, and changes to viral load by immune regulation were observed. An antibody, humanized HTLV-1 rat monoclonal antibody (hu-LAT-27), has both neutralization and antibody-dependent cellular cytotoxicity activities. In this study, we evaluated the preventive efficacy and potency of neutralizing monoclonal antibodies on HTLV-1 infection. CMs were administrated either with control IgG or hu-LAT-27 a day before infection and then CMs were intravenously inoculated with ATL-040. Proviral DNAs in peripheral blood and several tissues and organs were detected in control IgG-administrated CMs but not in hu-LAT-27 pre-administrated CMs during the experimental period. These results suggested that a monoclonal Ab, hu-LAT-27, prevents HTLV-1 infection in vivo and has the potential to be a prophylactic drug for HTLV-1 infection. In addition, the usefulness of the HTLV-1 CM model as an evaluation model for pharmaceutical development was demonstrated. Funding Sources Supported by the Japan Agency for Medical Research and Development, Strategic Center of Biomedical Advanced Vaccine Research and Development for Preparedness and Response, and the Japan Society for the Promotion of Science.