Researchers are investigating a new antiviral strategy which protects monkeys from SIV, a close relative of HIV. Elements of vaccines and gene therapy are used and experts say the development could lead to a vaccine for AIDS. Vaccines work by stimulating the immune system to recognize and attack a specific invader. However, several potential AIDS vaccines have failed to stimulate the immune system to produce antibodies that can stop HIV. Despite this, researchers have isolated a handful of antibodies from HIV-infected humans that stymie HIV in test-tube studies.
AIDS vaccine researcher Philip Johnson came up with a workaround: Bypass the immune response and just deliver the antibodies. The idea was tested in the monkey SIV model to see if it had promise. The researchers first created designer antibodies by linking together pieces of antibody to construct "immunoadhesins." These molecules derailed SIV in test-tube studies and can remain in the blood at high concentrations. They then stitched the genes for these immunoadhesins into an adeno-associated virus (AAV), a "vector" used in human gene therapy experiments to deliver foreign DNA into the body's cells. Nine monkeys received injections into their muscles of AAVs that carried three different immunoadhesins. Four weeks later, the researchers injected the monkeys with SIV. Six of the nine animals did not become infected, whereas all six control animals, which did not receive the immunoadhesins, did. Several practical questions still loom large. The three monkeys that were not protected by the immunoadhesins all had immune responses that attacked these artificial antibodies.
Researchers still do not know why did some monkey immune systems go after the designer antibodies whereas others did not.Additionally, unlike a vaccine, which builds long-lasting immunological memory against a pathogen, the designer antibody approach depends on the viral vector persisting and continuing to pump out the immunoadhesins. Although Johnson says the monkeys continue to produce the immunoadhesins 80 weeks out, it's unclear how long the AAV will survive. Another potential problem is that prolonged exposure to the immunoadhesins or the vector itself could lead to immune responses against them later. Then there's the question of SIV compared with HIV. They may be close relatives, but still differ in many ways. Lastly, the hurdles of testing in humans needs to be cleared before further studies can confirm its efficacy. In conclusion, despite all the limitations, this research could prove to be a boost to the thousands suffering from HIV infections.
