Getting closer to cracking HIV’s envelope protein

missing segment of HIV envelope could be target for HIV vaccine

For 30 years, researchers have tried to develop an HIV vaccine that would stop the virus from gaining a foothold in the body — before it attaches to T cells and slowly weakens the immune system.

“It has been extremely challenging to induce effective antibody responses against HIV-1,” says Bing Chen, PhD, who researches HIV’s molecular mechanisms at Boston Children’s Hospital.

HIV offers just one target for a vaccine to mimic to trigger protective antibodies: the envelope protein on its surface. Scientists have been struggling to capture the complex protein’s precise structure — and specifically, its structure before the virus fuses with the T-cell membrane.

That’s because once fusion happens, the protein undergoes several shape changes. An antibody targeting one of those later conformations would be less effective, since the infection would have already begun.

“Once the virus has fused to the cell, it’s too late,” says James J. Chou, PhD, a professor of biological chemistry and molecular pharmacology at Harvard Medical School.

A study led by Chou, Chen and Stephen Harrison, PhD, of Boston Children’s, has now found one of the last missing pieces of the envelope protein: the segment that anchors it to HIV’s outer membrane. Using a high-resolution imaging technique called nuclear magnetic resonance, the team captured the atomic structure of this segment, called the membrane-proximal external region (MPER). Their findings appeared earlier this month in PNAS.

The next step is to try to lock the MPER in its pre-fusion conformation and train the immune system to produce antibodies against the segment in animal models. Read more from Harvard Medical School.