GaJpin/DA/N2 IIIBenv 
OVERVIEW OF THE HIV-1 IIIBenv 
RETROVIRAL VECTOR CLINICAL PROGRAM 
HIV infection is the most rapidly expanding pandemic in recorded time. AIDS slowly 
and insidiously portends a more certain fatal outcome than even the scourge of medieval 
plague. Millions are infected today worldwide while tens of millions will contract this illness 
in the next few years. The rate of transmission is accelerating while the resources to control 
its spread diminish in many third world countries. 
The past teaches us that viral diseases posing threats of this magnitude can be best 
countered by the host immune system either on its own or with the help of either prophylactic 
or therapeutic immune stimulation. Roughly 75 separate HIV programs are in progress 
worldwide and nearly a dozen of these have progressed to clinical trials. However, no 
product has yet demonstrated clear effectiveness in either preventing or diminishing the 
advance of this dreaded disease. No product of this type has yet had human clinical approval. 
From their fundamental appreciation of HIV/AIDS viral genetics and immunology, most 
clinician-scientists believe that any effective product will need to not only elicit a specific 
antibody response, but must also activate a specific cell-mediated immune response. Patients 
with HIV/AIDS, for example, produce large amounts of antibody to their own illness, and yet 
most patients have only transient, relative protection from progression of their illness. It is 
the cellular immune arm of man which protects against malignancy and viruses such as HIV. 
It is here where the foundation of therapy must be directed and focused. 
A unique gene transfer-based approach for the treatment of HIV/AIDS has been 
developed. The traditionally effective approach represented by attenuated viral vaccines is 
simulated, but the historical hazard of virulent revertents is avoided. This is accomplished by 
molecular engineering, which provides genes coding for crucial immunodominant epitopes, 
yet only about half of the genetic information required to complete a functional HIV virion. 
The N2 IIIBenv vector programs uninfected antigen-presenting cells of the host to express 
crucial HIV ENV epitopes in a way that stimulates and/or enhances strong specific antibody 
and cytotoxic T cell (CTL) responses in mice and non-human primates in vivo. It stimulates 
CTL responses in human peripheral blood mononuclear cells (PBMC) in vitro. Critically, 
CTL reactivated in vitro have exhibited cross-reactivity on cells infected with a broad range 
of different HIV-1 strains and clinical isolates. 
The safety of this gene-transfer approach has been confirmed in mice injected with the 
retroviral vector in comparable routes and doses to the planned clinical trial with no evidence 
Recombinant DNA Research, Volume 17 
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