A clever story here where these folks out of Seattle and elsewhere have gone one step better on the lead of a well-known antibody that some people infected with HIV produce. The antibody, VRC01, neutralises most virus variants, but researchers have struggled to coax normal people to produce the antibody, since the necessary B-cell germ line is not easily roused to manufacture this antibody. At least not by simply dosing people with the gp120 viral protein that this antibody targets.
[A little background/reminder is that gp120, an HIV protein, binds CD4, a receptor on human T cells. It is the attendant destruction of such CD4-positive (CD4+ in the lingo) cells that ruins one's immune system: hence [virally] Acquired ImmunoDeficiency Syndrome.]
This VRC01 antibody—which would be key to a vaccine if one could force the body to produce it—binds gp120, but somehow in a different manner than CD4 binds it. It also importantly binds gp120 independently of the various variations in shape of the viral "spike" and its surrounding envelope constituents, thus maintaining its effectiveness in spite of all the devious manifold variations that HIV constantly throws up due to mutating rapidly.
Now then, the above researchers have taken gp120 and whittled it down cleverly to the tiniest fragment they could achieve that still binds VRC01. This little fragment should in theory then be a potent little immunogen since there's not much to it other than the bit that should stimulate VRC01 production.
Seemingly just whittling it down wasn't enough: these folks then assembled the fragment into virus-like nanoparticles of 60 or so fragments, and those pseudo-virii apparently stimulate, in vitro, the right kind of B cell! So, bravo, and their next step is to try this in animals that have been engineered to produce human type antibodies.
Why Nanoparticles?
One might ask: why the virus-like nanoparticle? I can only guess that this gives the collection of viral epitopes some biological plausibility to the B cells in charge of deciding whether to commit to production of antibody. You will frequently see cartoon models of antibody functioning, or cell receptor binding, that depict human cells as giant spheres, and proteins binding to receptors in a binary fashion as keys bind to a lock. But no doubt, this is a crude oversimplification. I can well imagine that one viral antigen fragment might not get a germ-line B-cell "excited", but a nanoparticle resembling a virus particle might interact differently with the surface of the cell recognising it. Perhaps the recognising cell wraps around it in a sort of pocketed embrace, and multiple receptors interact with the particle and realise it's a viroid. A sort of cellular version of the blind-men-and-the-elephant [weak] "joke".I am just speculating above, but this could be a case of an intelligent breakthrough being based at least in part on a rejection of the cartoonish idea that human cells are spheres, and protein-protein interactions occur in separate, standalone binary fashion like a field full of independent padlocks and keys.
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