What it means to find a “weak spot” in HIV

What it means to find a “weak spot” in HIV
This week, researchers from the National Institutes of Health reported that they’ve found a new “weak spot” in HIV that they hope to be able to exploit to design an effective vaccine.

that they’ve found a new “weak spot” in HIV that they hope to be able to exploit to design an effective vaccine. It’s an exciting proposition, as the disease continues to ravage people around the globe while confounding efforts to create an effective cure. This breakthrough wouldn’t lead to a cure for those already infected, but it could dramatically slow the spread of the disease to new people.

The study looked at the antibodies present in an unnamed patient, finding a very strong binder to the HIV viral capsids called VRC34.01 , part of a group called broadly neutralizing HIV antibodies (bnAbs). They found that it is effective at stopping HIV from infecting cells, meaning that if they can design a vaccine to prompt the body to release this antibody, it’s possible they could cheaply make most or all people immune.

What’s most interesting is that these antibodies seem to bind to the so-called “fusion peptide” that allows the virus to fuse with and enter a cell. That’s important because the fusion peptide is very short, only eight amino acids long. This means that there’s not much room for evolution to screw with the sequence — changing any one animo acid changes 12.5% of the overall sequence, likely making fusion impossible.

This means that VRC34.01 can rely on an unchanging target sequence. And since this fusion peptide must get right up close to a cell surface in order to work, the virus can’t just grow a big bump to physically block the antibody from getting in. Though HIV is legendary for its ability to quickly evolve in response to a medicine or any other pressure, even it can’t survival-of-the-fittest its way out of certain multi-faceted problems.

That’s what makes this a “weak spot” — past miracle cures like AZT work for a while, but HIV always finds a way to modify or live without the specific structure involved in the drug’s action, and so eventually patients stop seeing benefits from the drug. By targeting a sequence that HIV cannot modify or hide away without making itself useless, the hope is that this could be the perfect defense mechanism.

The antigen stimulates release of the antibody — so now these scientists need to find an antigen that corresponds to the newly discovered antibody.

The thing about antibodies is that they do their work in the areas between cells, which means they can stop viruses from getting into cells, or between cells, but once genetic material does get inside a cell, it’s in there. So these antibodies will do nothing for HIV positive people, but they could provide yet another means to partially repress the spread of the virus within the body. It’s this spread that causes HIV to become “full blown” AIDS, and keeping that spread slow and the “viral load” low is important to keeping HIV positive people from developing symptoms.

Like cancer research, HIV research has had so many “breakthroughs” that people naturally get cynical about any progress seemingly made toward a wide-ranging cure. But these sorts of partial cures have turned HIV from an assured, and quite proximate death into a dangerous but manageable disease, like diabetes. Between management of infected people, and prevention of further spread of the infection, it should be possible to effectively “cure” the disease, or at least its symptoms.

One interesting side note is that HIV is very similar to the hijacked viruses that deliver engineered genes in advanced biological experiments and bleeding edge medical treatments. Could a therapy like this make an HIV-positive person immune to potentially life-extending gene therapies, as well?