New antibody may fight HIV virus more effectively

Scientists have identified a novel antibody that could more effectively detect and neutralise HIV virus in an infected patient.
Proteins called broadly neutralising antibodies (bNAbs) are a promising key to the prevention of infection by HIV, the virus that causes AIDS.
The bNAbs have been found in blood samples from some HIV patients whose immune systems can naturally control the infection.
These antibodies may protect a patient's healthy cells by recognising a protein called the envelope spike, present on the surface of all HIV strains and inhibiting, or neutralising, the effects of the virus.
Researchers at the California Institute of Technology have discovered that one particular bNAb may be able to recognise this signature protein, even as it takes on different conformations during infection - making it easier to detect and neutralise the viruses in an infected patient.

The process of HIV infection begins when the virus comes into contact with human immune cells called T cells that carry a particular protein, CD4, on their surface.

Three-part (or "trimer") proteins called envelope spikes on the surface of the virus recognise and bind to the CD4 proteins.
The spikes can be in either a closed or an open conformation, going from closed to open when the spike binds to CD4.
Last year, Pamela Bjorkman, Centennial Professor of Biology and her collaborators at Rockefeller University reported initial characterisation of a potent bNAb called 8ANC195 in the blood of HIV patients whose immune systems could naturally control their infections.

They also discovered that this antibody could neutralise the HIV virus by targeting a different epitope than any other previously identified bNAb.
Researchers found that although most bNAbs recognise the envelope spike in its closed conformation, 8ANC195 could recognise the viral protein in both the closed conformation and a partially open conformation.
"We think it's actually an advantage if the antibody can recognise these different forms," said Louise Scharf, a postdoctoral scholar in Bjorkman's laboratory.
A potential medical application of this antibody is in so-called combination therapies, in which a patient is given a cocktail of several antibodies that work in different ways to fight off the virus as it rapidly changes and evolves.

"So 8ANC195 is one more antibody that we can use therapeutically; it targets a different epitope than other potent antibodies, and it has the advantage of being able to recognise these multiple conformations," said Scharf.
The idea of bNAb therapeutics might not be far from a clinical reality. Scharf said that the same collaborators at Rockefeller University are already testing bNAbs in a human treatment in a clinical trial.
The study was published in the journal Cell.