Promising target for AIDS vaccine identified

A new research by Dana-Farber Cancer Institute scientists have indicated that a section of the AIDS virus's protein envelope once considered an improbable target for a vaccine now appears to be one of the most promising.

The section, a twisting strand of protein known as the V3 loop, is an attractive vaccine target because immune system antibodies aimed at the loop may offer protection against multiple genetic subtypes of HIV-1, the virus that causes AIDS.

This is a key prerequisite of any AIDS vaccine because the viruses mutate rapidly and by now comprise millions of different strains that are grouped into different genetic subtypes, or "clades."

In the study, the investigators injected a monoclonal antibody -- a preparation of millions of identical antibodies that fight viral infection -- into Asian monkeys known as macaques.

The antibody came from a person infected with a specific clade of HIV-1. The macaques were then exposed to virus of a different clade.

The investigators knew that the antibody would latch onto a portion of the virus's V3 loop, potentially barring the virus from invading nearby cells, but they did not know whether it would prevent infection from a separate subtype of the virus.

The results were striking: All the treated monkeys were protected from infection by the monkey form of HIV-1, known as SHIV.

Monkeys exposed to the virus without receiving the monoclonal antibody, by contrast, became heavily infected.

"This is the first time a monoclonal antibody made against an AIDS virus of one clade has provided complete protection against an AIDS virus of a different clade in animal models," said senior author Ruth Ruprecht, of Dana-Farber.

 "Previous studies have shown that such neutralizing antibodies can protect macaques from infection within one clade; but as more clades of the AIDS virus evolve, it has been unclear whether such antibodies could shield across different clades and prevent infection. Now we have an answer," she added.

The antibody treatment technique used in the study is unlikely to confer long-term protection against HIV-1 because the infected antibodies do not remain active in the body for very long.

The value of the study is that it demonstrates that antibodies directed against the V3 loop of one clade of HIV-1 can create an immune system shield against another clade.

The researchers' findings are published online in the Public Library of Science journal PLoS One.