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Tuesday, November 25, 2003

Brad Delong is trying to understand what the post immediately below means. There I typed Brad Delong so my hits should spike. He is very polite. I fear that the less charitably inclined are wondering if I have gone nuts. I mean do I really imagine that there is no real biologist around who either is doing what I propose or knows why it is a bad idea ? Well no I don't, but hey this is my blog.

I tried some more background for him and I include it here in case anyone else is reading the M-13 meets HIV thread.

OK so what is the idea.
So far AIDS vaccines are not working. This is not a surprise, since AIDS doesn't seem to be the kind of disease for which a vaccine works. The first symptom is an immune response yet people usually succumb in the end. It is now known that the immune system does slow the progress of HIV. However it does it in the less well known way -- by killing HIV infected cells. That is, in addition to the "ordinary" humoral immune response of making antibodies which stick to nasties and then cause them trouble, there is also the cell mediated system in which Killer T-cells kill our cells if they have strange proteins on them. This is useful to zap cancers (people only get cancer when this fails) and to kill virus infected cells.

It is not enough to clear HIV from the infected person. Recall HIV makes a DNA copy of its genome and puts the copy in a host cell chromasome. Sometimes the HIV goes dormant for a while. It stops making proteins so there is no way to tell if it is there. Anyway so it appears accoding the the last thing I read.

Now vaccines do stimulate anti HIV responses but what has an effect is the killer cell zap cells infected with HIV which HIV is active. Vaccines also cause us to make the usual pointless antibodies which don't do much of anything to the HIV.

Effective vaccines stop viruses by keeping them from infecting our cells. That is we make an antibody which sticks to the part of the virus which sticks to our cells to infect. That way the antibodies prevent infection in the first place.

So the question I ask is why don't HIV infected people (or vaccinated people) make antibodies which block infection ? One possibility is that there is no such antibody. Humans can make a huge variety of antibodies but not an infinite variety. If so I have nothing more to say.

It is also definitely possible that humans can make such a blocking antibody but don't when vaccinated or HIV infected. This is possible because antibody production requires more than a B-cell (the antibody producing cells) which makes the appropriate antibody and the target. There is a complex process involving 3 cells which communicate the antibody presenting cell presents the target antigen to the helper t-cell and the helper t-cell presents the antigen to the B-cell which makes the antibody which sticks to the antigen. At each stage there are a number of complex partly understood processes designed to prevent autoimmunity (our immune system attacking us).

I hope that the problem with making an antibody which blocks HIV infection (by sticking to the same bit of HIV which sticks to target cells) is at the level of the antibody presenting cell or the helper t-cell.
If so it might be possible to get around it by making a vaccine of a hybrid protein which contains the right bit of HIV and another protein to serve as a handle for the antibody presenting cell and the helper t-cell.

So the question my proposed experiment attempts to address is can humans make an antibody which causes HIV to fall off its target ? If so one might hope to diddle with the vaccine so as to get something which stimulates production of this antibody. Thus weird other ways to look for antibodies which do something. In this case bind to HIV and make it fall off of its target (CD4).


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