Presently 1.2% of babies born in New York City hospitals are born to HIV infected mothers, and the number is likely to increase nationwide. Up to one third of these babies will become infected unless a prevention strategy is developed. Passive immunization with polyclonal HIV immune globulins (HIVIG) and monoclonal neutralizing anti-HIV antibodies has been shown to prevent HIV infection in chimpanzees. However, limitation in the number of chimpanzees available has prevented the optimization of passive immunization schedules. The goal of the present study is to use a small animal model, the Hu-PBL-SCID mouse to provide information relevant to the design and improvement of clinical trials aimed at preventing vertical transmission of HIV, and to define conditions for prophylaxis after accidental HIV exposure. Severe combined immune deficient (SCID) mice will be engrafted with human peripheral blood lymphocytes (PBL) and subsequently infected with HIV. Initial studies will assess the dose requirements for protection of these animals by. passive immunization with HIVIG against both laboratory isolates of HIV-1, and against primary patient isolates. Infection will be assessed by virus isolation in co-cultures of spleen and peritoneal cells harvested from treated mice, and by PCR for HIV sequences in these cell populations. If HIVIG is efficacious in clinical trials, it will inevitably be in short supply. Thus, it is important to attempt to develop a substitute for HIVIG composed of an appropriately designed mixture of monoclonal antibodies. The present study will evaluate neutralizing monoclonal antibodies to the V3 loop and CD4 binding domain of the HIV-1 envelope, and to neutralizing epitopes on gp4l, for their ability singly, and in combination, to provide optimal post-exposure prophylaxis of HIV-1 infection.
| Andrus, L; Szabo, P; Grady, R W et al. (1998) Antiretroviral effects of deoxyhypusyl hydroxylase inhibitors: a hypusine-dependent host cell mechanism for replication of human immunodeficiency virus type 1 (HIV-1). Biochem Pharmacol 55:1807-18 |
| Andrus, L; Prince, A M; Bernal, I et al. (1998) Passive immunization with a human immunodeficiency virus type 1-neutralizing monoclonal antibody in Hu-PBL-SCID mice: isolation of a neutralization escape variant. J Infect Dis 177:889-97 |
