Discoveries at the Institute
Research uncovers target for HIV-1 vaccine
An infected white blood cell from an AIDS patient.
Of the many mysteries about HIV-1, the virus that causes AIDS, a particularly puzzling one is why immune system proteins called broadly neutralizing antibodies (BNAbs) seem to make only a halfhearted attack on the virus. In a recent study, Dana-Farber's Ellis Reinherz, MD, and colleagues found that part of the answer lies in the folds of the virus's protein coat.
Normally, broadly neutralizing antibodies make a beeline for harmful viruses such as HIV-1 based on protein "ID tags" on the viral surface. The new study focused on a surface region called MPER, which is found on many different strains of the virus. Such regularity should make it an attractive target for BNAbs, but their assault turns out to be rather mild.
The Dana-Farber team discovered that this is because much of MPER is sheltered inside the viral membrane, concealing it from the immune system. However, they found that a BNAb called 4E10 targets a key section of MPER and pulls out portions that had been buried in the membrane. By latching onto these areas, 4E10 blocks the virus from invading white blood cells, halting the infection process at its outset.
Says Reinherz, "The discovery may open the way to BNAb-based vaccines that would be effective against many strains of HIV-1."
