HIV Vaccine

[Marko Schmarko]

This is my first attempt at fulfilling Rduke's desire for more science.

I just started working at The Scripps Reserach Institute in La Jolla, CA in an HIV lab that solely concentrates on antibody-HIV interactions in an effort to, eventually, produce a vaccine.

The issues with this approach are numerous. The most daunting, though, is that there is a sort of point-of-no-return with HIV. Once the virus has effectively implanted its genome into the victim, the immune system is useless. HIV's genome mutates so rapidly that if it is given the chance to replicate at all, it will quickly evade any individual antibody, and broadly incorporate itself within a week.

The challenge, then, is to prep the body to mount a sufficient mass of antibody to neutralize the virus before it has the chance infect.


My question:

Does this approach seem viable? Will the body ever be able to mount sufficient concentrations of antibody before infection? Will HIV simply evade the antibod(y/ies) used?

[Rduke55]

Yay! Although i was thinking about more of a summary, followed by any open questions (since most of us won't know much about the subject)
I'll do mine tomorrow as I'm waaaayyy too hungover to form reasonable thoughts today (Steeler's rule /images/graemlins/tongue.gif).

Marko, I'm pretty ignorant about the specifics of HIV. Does the virus circulate for a time before it actually gets into a cell? When it replicates, do the viruses get into circulation?
And I would guess that it can't mutate all it's surface proteins. Do we just need to find one that stays the same?

[Marko Schmarko]

Yes, it circulates for a bit before infection... I'm actually unsure as to exactly how long, but I believe it's about a week before it's well-incoroporated.

Once it replicates, there viruses do circulate.

It can mutate all its surface proteins, unfortunately. Obviously not entirely, but antibodies generally target only small portions of the proteins, so you can drastically affect the affinity of the antibodies with only small mutations. [This has been conclusively shown with serial mutations of the proteins.]

[Rduke55]

But aren't surface proteins fairly large? So if it's just changing a small part of it, and the antibody recognizes a small part, then woudn't the chance that the virus mutated the section of protein that the antibody recognizes be pretty small?

Man, that sentence makes my brain hurt.

[Rduke55]

Also, do you know anything about the other therapies that are promising besides a vaccine?

[Brom]

I saw a special on Discovery channel that said that humans would eventually evolve an immunity to HIV. It cited Africa as an example. With the huge number of HIV infected people there, coupled with abundant breeding, some people have actually developed a natural immunuty to the disease. This immunity is appearing in more and more future generations at an exponential rate, yet scientists are unable to distinguish how they are accomplishing it.

Did anyone else see tnis special? Does anyone know more about this? Because I think it is very interesting.

[Marko Schmarko]

[ QUOTE ]
But aren't surface proteins fairly large? So if it's just changing a small part of it, and the antibody recognizes a small part, then woudn't the chance that the virus mutated the section of protein that the antibody recognizes be pretty small?

[/ QUOTE ]

This is a common misconception. Every individual nucleotide mutates indepedently at a certain rate [a very high one in HIV]. Thus, as size increases, absolute mutation increases proportionally.

[Marko Schmarko]

[ QUOTE ]
Also, do you know anything about the other therapies that are promising besides a vaccine?

[/ QUOTE ]
Well, honestly... not really.
The current broadly-distributed cocktails mostly consist of anti-retroviral drugs to stop the virus from incorporating itself, and anti-protease viruses to stop the virus from the destroying the CD4 proteins. [This is from my ever-flakey memory, so I could be wrong.]

These treatments have proven effective in prolonging the span of the disease in infected patients and also in preventing the incorporation of the viral genome in the first place, but the latter requires that you suspect that you may have been infected. I would imagine most victims are unaware, or at least not concerned enough to go to the doctor.

I wonder if there is some way to trigger in-vivo anti-retroviral secretion.

[Marko Schmarko]

[ QUOTE ]
I saw a special on Discovery channel that said that humans would eventually evolve an immunity to HIV. It cited Africa as an example. With the huge number of HIV infected people there, coupled with abundant breeding, some people have actually developed a natural immunuty to the disease. This immunity is appearing in more and more future generations at an exponential rate, yet scientists are unable to distinguish how they are accomplishing it.

[/ QUOTE ]

I have never heard of people being immune to HIV. There are some that are long term survivors, but this isn't really the same thing as immune.

The serum of long-term survivors has been placed under a great deal of study, and is so far relatively infertile. It is from this serum that a great deal of antibodies have been isolated, but it's proven difficult to duplicate the donors' virility.

[erby]

I worked one summer in college with Hemispherx Biopharma in Philadelphia. They were looking into the use of broad range antivirals, specifically Interferon alpha and their own trademarked drug Ampligen. They showed some promising effects, however the company really didn't have their sh*t together.

ERBY /images/graemlins/spade.gif

[FredBoots]

I'm surprised at the amount of research on HIV, given the miniscule number of people it kills. The number of dead from AIDS last year in Canada was like 60 people. Heart disease kills 80,000 / year.

I guess you could sell it to Africa -- can they afford it? -- but I'm not convinced that what is happening in Africa is AIDS.

[Marko Schmarko]

Yes, but HIV is awesome. Much more awesome than fat, lazy people clogging their arteries.

[Marko Schmarko]

Bump.