USS Clueless -- Prospects for an HIV vaccine

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Prospects for an HIV vaccine

Unfortunately, they're extremely poor. Even if they produce one, it's unlikely to be of any use. But to explain why I'm going to have to introduce a lot of background, because you have to understand how viruses work, how our bodies defend against them, what a vaccine does. Then I'll have to talk about how HIV works and how it is unusual.

Whenever anyone tries to define "life", the virus always straddles the dividing line between living and unliving. Looking at its behavior without knowing what it is, it seems to act as if it were living. But in actuality it's little more than a protein coat surrounding some nucleic acids. It doesn't have the ability to do anything we would refer to as "live" on its own; it's completely static when it's outside a cell. The protein coat defends the nucleic acids inside, and also facilitate entry through the wall of a cell which it will try to infect. Once inside, the coat bursts and releases the nucleic acids. These then take over the cell's normal processes and use them to create new viruses. Eventually this kills the cell but only after thousands of new viruses have been created. The cell bursts, spilling the viruses back into the blood to infect other cells. Some of the viruses will be shed into the environment in any of a number of ways, to infect other creatures.

Our bodies contain elaborate defenses against this kind of thing. First, there are cells whose job is to detect that an invasion is in process. When one of them discovers this, it uses a genetic toolbox of about a thousand DNA fragments, and through mechanisms which are not yet well understood it will figure out the genetic description of an appropriate antibody. This is really a custom protein which has a section on one side which is exactly the right shape to connect to something on the invader, which is called an antigen. Once the white cell gets it right, it will start reproducing like mad, creating and releasing antibodies and also creating certain signal hormones to alert the rest of the body that an attack is in progress.

Then there's a pitched battle. Antibodies connect to the invaders, which not only deactivates them if they're viruses but also tags them so that other white cells can engulf them and destroy them with enzymes.

The recognition process is slow. From initial infection it typically takes three days for one or more white cells to get the combination right. After that, they reproduce over a period of a few hours and then battle is joined.

During that initial period, the invading virus is free and clear to do what it will. So it reproduces and its numbers grow exponentially. By the time the immune system is ready for battle, there are a lot of viruses. So eradicating them takes a while. How long it takes depends on the virus in question.

Now it's important to understand the underlying design philosophy behind all this: it all assumes that there's a threshold viral load which is not dangerous, and it only girds for a fight when the load exceeds that amount. When you "get over" a cold, it's not the case that you have no viruses left. Rather, you have so few that they no longer represent a danger to you. The body can't remain in full-scale battle mobilization over long periods; it would seriously harm other things and could kill you. So it gears up when an invasion starts, but stands down once most of the battle is won.

But not totally. After the battle ends, some of the T4 cells, the ones which recognize an invader and create antibodies, remain behind. The immune system has a kind of memory about this, embodied in T4 cells which have already adapted to recognize invaders.

If you are ever infected again with a virus you've already had, the immune system is ready to go. Instead of taking three days to recognize the invasion, the T4 cells already knowing about it start reproducing immediately, producing antibodies. It cuts a process which ordinarily takes maybe three days to less than six hours. And since the number of viruses grows exponentially, it means that the peak viral load in your blood will only be a fraction of a percent of what it would otherwise have been. Indeed, this response is so fast and so efficient that you won't even realize that you've gotten sick again.

But with some viruses, there is substantial damage done before the immune system gets ready for the fight, and in some cases the victim can die. In some cases it takes a lot longer to recognize the invader, for instance. The most fatal disease known in humans is rabies. Everyone who gets rabies and isn't treated for it will die from it; fatality rate is 100%. This is greater than Ebola, which has a fatality rate of about 95%, or Marburg, about 70%.

That's where vaccines come in. The first vaccine was developed nearly three hundred years ago, to fight smallpox. But it wasn't until late in the 19th century that they began to even get an idea how they worked, and they didn't really become practical until early in the 20th century.

A vaccine is, in essence, a benign disease. Its purpose is to introduce antigens into your body which are close to those on a real disease you haven't had. By doing this, your body goes through that three day recognition-and-create-antibody process, only to find that there's nothing to fight. Still, primed T4 cells remain afterwards, and if you then get infected for the first time with the disease, your body reacts as if it had already had it. The response is rapid and effective and the viral load never gets great. In most cases, again, you won't even realize you've been infected.

But you are infected. That's the critical point. A vaccine doesn't keep you from getting a disease. What it does do is make it so that your body responds to the disease far more rapidly so that the peak viral load is vastly lower, which means that the virus has far less opportunity to do permanent harm.

HIV is a ferocious disease with truly pernicious strategies. Viruses do all sorts of weird things, and HIV is one of the worst. It's actually not very infections; unlike adenoviruses it is killed by exposure to oxygen, for instance. So it can only pass from one person to another in body fluids, primarily blood and sexual secretions. It cannot be passed by casual contact.

But it can be passed by a number of other activities, like sex and sharing hypodermic needles.

When you get HIV, it initially acts like any other virus and starts to reproduce by entering cells, taking over their systems, making lots of viruses, killing the cells and bursting back out into the blood.

Your body recognizes this and mounts an immune response just as it would against a cold and flu. In a few days T4 cells have recognized the disease and started creating antibodies against it, and you have a battle which the immune system wins. You get over the disease!


But, during that time, HIV plays its trump card. HIV is a "retrovirus" which means that in addition to its normal life cycle, it has the ability to transcribe its genetic information into the cell it infects. In some cases this happens without the cell reproducing viruses, and such an infected cell is a timebomb. There are no viruses in it, but if in future that genetic information gets activated then the cell will start creating HIV. And most insidiously of all, it does this preferentially to the T4 cells, the point men of the immune system.

So what happens is that after the first infection, when HIV hit a high blood load and then collapsed, it becomes chronic. Most of the immune response to it goes away, and it achieves a low but continuous level in the blood. Good enough, by the standards of the immune system; that's the goal. There are a small number of viruses and a low level of activity against it, and the viral load is low and stays low. Every once in a while, one of the transcribed T4 cells activates and starts producing HIV; this kills the T4 cell, which burst and spills a small pulse of HIV into the blood stream. The immune system kills most of them, but a few manage to find and infect other T4 cells, transcribing their information into the chromosomes.

So over a long period of time, the number of T4 cells declines because they're slowly being destroyed by HIV. Eventually there are too few to make any difference. Without T4 cells, the rest of the immune system is useless; they never see a signal indicating that there's an infection, so they never respond to it. The patient has AIDS, and there's no hope.

The problem is that the fundamental assumption of the immune system is wrong for HIV: there is no safe level of the virus. Any level will eventually kill you.

So what if we have a vaccine? Well, the immune system would be preprogrammed to recognize HIV which would speed a response up from three days to six hours. But during that six hours the virus would still be reproducing, and at least some T4 cells would get infected. Then the immune system would stomp on the others. The patient would not notice an infection -- but an infection would take place nonetheless. So all that happens is that the patient skips the initial big pulse of viruses and goes directly into the second stage of chronic low-level infection which slowly destroys the immune system. How is this really better?

The vaccine would not prevent AIDS, because a vaccine doesn't prevent infection. It keeps the viruses from getting above a dangerous threshold -- except that for HIV, there appears to be no safe level of the virus.

So why are they working on one? Because there isn't anything else they can do. Modern medicine is very impressive, but it's largely based on a relatively small number of basic discovery. Really very few, and of those only one is effective against viruses. Antibiotics, for instance, are useless against viruses. Antibiotics are selective poisons which interfere with certain cell functions, and they happen to be functions present in bacteria but not in us. So if you've got syphilis and you take penicillin, it doesn't affect you but it kills the bacteria which have infected you. That's because the bacteria really are alive, and penicillin interferes with essential life functions.

But a virus really isn't quite alive; when it's not in a cell it doesn't have any life function. It's just information; the life comes from the cell it infects and takes over. So chemical poisons have no effect on it; there isn't anything to poison.

Only vaccines work, and they've performed miracles. Indeed, the granddaddy of them all, vaccinia, was used to completely eradicate for the very first time in history a disease which has afflicted humans all through recorded history. It's a modern miracle: for at least ten years there hasn't been a single case of smallpox anywhere on earth, and there won't ever be again.

 But for nearly all known diseases, there is a threshold of infection which is not dangerous. What a vaccine does is to keep the disease below that threshold.

If a vaccine doesn't work against HIV, then nothing will. Antiviral drugs aren't quite like antibiotics and there's strong evidence that they don't cure. A victim has to take them forever and even then eventually the disease will kill them. Antiviral drugs are also expensive and have to be taken several times per day. If a vaccine works, it will be a one-time treatment which could be administered even before infection to prevent it.

If it works -- only it won't. But the researchers don't want to surrender without a fight, so they're trying it anyway in hopes that there will be a miracle. I don't think there will be.

The only solution for HIV is prevention, and that's unlikely. This plague is with us for the long haul; it's going to be, in the long run, one of the great killers of humans. The history of the 21st century will be changed by it, just as the history of the 14th century was changed by Bubonic Plague (the "Black Death"). And it will take a breakthrough in theory to do anything about it. Right now no-one knows what that might be.

I don't like this answer, but the universe didn't promise to please me.

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