HIV Immunotherapeutic Vaccines

Abstract

New combinations of antiretrovirals have improved the quality of life and length of survival of patients with HIV infection and AIDS, but they have significant disadvantages. These include considerable toxicity, the development of drug resistance and expense. Successful immunotherapeutic vaccination against HIV would overcome these problems. None of the approaches that have been tried so far have shown a sufficient effect on HIV replication or on immunorestoration to merit their introduction to clinical practice. The most developed agent thus far is Remune, a gp120 depleted whole killed HIV-1 vaccine that has shown marked cytotoxic T lymphocyte responses when administered to man. CD4 count and HIV-1 viral load responses have occurred, but have so far been disappointing in their magnitude. Remune is entering Phase III trials in North America, Europe and the Far East, to determine clinical efficacy. Immunization using recombinant HIV envelope proteins, such as rgp160, for example with VaxSyn, have failed to produce a therapeutic response. Similarly, agents using HIV core antigens, such as p24VLP, have also failed to work. Hence, newer strategies have been tried. Recombinant canarypox vaccines like ALVAC 1452 and highly attenuated vaccinia virus vaccines, such as NYVAC, have been used in combination with HIV genes and peptides. Preliminary results suggest that they might reduce the HIV replication rate, but this needs confirming in larger clinical trials. DNA vaccination has produced encouraging results in monkeys, but the success has not yet been repeated in humans. Other strategies at an early stage include the exploitation of the protective alloimmune response in man. Outside the immunotherapeutic area, other promising new strategies that are being developed in parallel, include the fusion inhibitors, such as T-20. The potential benefits from a successful immunotherapeutic vaccine dictate that this area should, and will receive priority.