A research team may have broken the impasse that has frustrated HIV vaccine researchers by using an unconventional approach that bypasses the usual vaccine development path. Using gene transfer technology to produces molecules that block infection, the scientists protected monkeys from infection by a virus closely related to HIV — the simian immunodeficiency virus, or SIV. “We used a leapfrog strategy, bypassing the natural immune system response that was the target of previous HIV and SIV vaccine candidates,” explains study leader Philip R. Johnson, MD, chief scientific officer at The Children’s Hospital of Philadelphia and professor of pediatrics at the University of Pennsylvania. Johnson and colleagues reported their work in Nature Medicine Most attempts at developing an HIV vaccine have used substances aimed at stimulating the body’s immune system to produce antibodies that would eliminate the virus before or after it infected cells. In clinical trials, however, these vaccines have not elicited protective immune responses, just as the body fails on its own to produce an effective response during natural HIV infection.

Johnson’s approach was divided into two phases. In the first phase, researchers created antibody-like proteins, called immunoadhesins, which were specifically designed to bind to SIV and block it from infecting cells. Once proven to work against SIV in the laboratory, DNA representing SIV-specific immunoadhesins was engineered into a carrier virus designed to deliver the DNA to monkeys. The researchers chose adeno-associated virus (AAV) as the carrier because it’s an effective way to insert DNA into the cells of a monkey or human. In the second part of the study, the team injected AAV carriers into the muscles of monkeys, where the imported DNA produced immunoadhesins that entered the blood circulation. One month after administration of the AAV carriers, the immunized monkeys were injected with live SIV. The majority of the immunized monkeys were completely protected from SIV infection, and all were protected from AIDS. In contrast, a group of unimmunized monkeys were all infected by SIV, and two-thirds died of AIDS complications. High concentrations of the SIV-specific immunoadhesins remained in the blood for more than a year.

The researchers cautioned that additional studies must be conducted before the technique can be translated into an HIV vaccine for humans, which could still be years away. “To ultimately succeed, more and better molecules that work against HIV, including human monoclonal antibodies, will be needed,” they report. In the meantime, the technique may have potential use in preventing other infectious diseases, such as malaria.

Source
Science Daily

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