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peHRG214 - Clinical Trial in Texas

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dario:

--- Quote from: J220 on July 09, 2006, 12:27:10 AM ---
Goats rule.

--- End quote ---

J220,
I like this! It is funny!  Imagine all of us (as you already said) shouting Baaaah! 

Joking apart, I am still very sceptical of the whole idea of using goats to derive polyclonal antibodies to "hunt" not only the virus but even infected cells (I am also curious if this would mean the latent cells as well) ...

I know that animals were used in the past to derive antibodies that effectively cured illnesses affecting humans.  I am not sure if it was smallpox or something else.  But I am still suspicious ... How on earth could something useful be derived from such stubborn animal as goats? Maybe I am saying this "illogical" thing because I remember grandpa's small herd of goats.

ScienceGuy25 works in the field of immunotheraphy (working on his Phd) and says that the idea is not all far-fetched.  Maybe he can explain why.

As J220 says ... GOATS RULE ... but I prefer sheep!

J220:
I think it makes perfect sense, in my opinion.

Humans do not have the proper antibodies to do the job, so if we find the antibodies in an animal, any animal, that does the trick then that will work.

As far goats being stubborn? Heck, maybe that's why they have such strong antibodies! Ha ha ha ha....oh sorry, bah bah bah bah bah. J.

I think my signature from now on will be:

Goats rule (plus my icon!). Better than nothing I suppose :)

ScienceGuy25:
Hey Dario (and others)

As I said i unfortunately haven't had a lot of time to reserach this particular therapy but I can tell you a little bit about the basics of immunotherapies like these.  Obviously we know that the human antibody response is insufficient to control HIV and so looking to other mammals (who all have relatively similar immune systems as humans) is not at all as wild and crazy as it sounds.  I believe much of this got started becase there was some evidence out there from a goat virus that infects goat macrophages and monocytes and was also found to infect some humans who drank goat milk.  I believe this goat virus caused some minor problems for humans but was also found to infect other humans and be fairly inert.  They found that human antibodies made against this virus had some cross reactivity with HIV, i believe by binding to GP120 (but don't quote me on all of this i haven't had time to read enough about it)

Anyways that company Virionxy realizing that goats had a natural virus which infected their macrophages and moncytes like HIV decided to expose the goats to HIV and see what their response was.  Interestingly, the goats seemed to mount a stronger response to the virus than humans.  The goat antibodies recognized a variety of "epitopes" on the virus that humans seem to ignore. Essentially the goat antibodies were just a lot better at recognizing and neutralizing the virus and virus infected cells.

Antibodies are relatively simple molecules, they consist of a framework region that at least in mice can be "humanized" so that they can be put into humans without our immune system recognizing the molecules as foreign and attacking them.  I would guess this company has a similar technology to "humanize" these goat antibodies so that they can be safely given to human.  Since they've already passed phase I trials, they've proven their goat antibody is safe in humans and now they can start to look a little bit more at efficacy. 

As to your question about latent infection, i'm not 100% sure, it depends if the latently infected cells are expressing epitopes that the antibody can recognize. I don't know enough about HIV latent infection to answer that but I'll check.

Here's a new article published explaining the basics, i'll read it when i get time and see if i can offer anything else.

Cheers,
ScienceGuy



Broad neutralization and complement-mediated lysis of HIV-1 by PEHRG214, a novel caprine anti-HIV-1 polyclonal antibody.

AIDS. 2006 Apr 24;20(7):1093-4.

J220:
Here is the link to the full article which Scienceguy referred to :

http://www.nrl.gov.au/dir185/NRLAttach.nsf/Images/McPheeD.pdf/$File/McPheeD.pdf

It's pretty straightforward, the premise. I went ahead and wrote to the company asking them if they could talk a bit about latent infection. We'll see if they reply.

In tne meantime, this is the overview of the substance, from their website:

The main points of difference between PEHRG214 and other HIV drugs are:

• Unique mechanism of action: The mechanism of anti-viral action of PEHRG214, which neutralises and inactivates the virus, differs from that of other anti-HIV treatments. Adding drugs of different modes of action to current combination therapies makes treatment of HIV more effective. With its unique anti-HIV mechanism, PEHRG214 provides the opportunity to enhance efficacy when added to standard drug treatments. 

• Disguise: PEHRG214 targets HIV epitopes that do not naturally stimulate the human immune system thereby circumventing one of HIV’s most effective means of defence – disguise. 

• Mutation: PEHRG214 binds to a number of sites on HIV which should hinder the virus’ natural ability to evade the drug by mutation. This is being carefully evaluated.

• Polyclonal: Therapies based on monoclonal antibodies suffer from the same problem as conventional drugs in that they only target one site on the virus. PEHRG214’s polyclonal antibodies enable it to attack a number of sites simultaneously thus increasing its likely effectiveness.

• Focus of attack: PEHRG214 provides antibodies produced externally and delivered to the patient through passive immunotherapy, thereby enabling the patients own immune system to reconstitute.


The disguise part seems to refer to latency. As far as I understand it latent infected cells seem, to the human immune system, like healthy cells, and that is why they persist . It's evident that Virionyx has discovered that the goat hiv antipbodies does recognize these latent infected cells, thanks to epitopes that are invisible to the human body.

ScienceGuy25:
Hey J220

You could be right on the latency thing.  You probably know lots of virus have two life cycles, lytic or latent.  Lytic they're actively reproducing and this creates many epitopes that an immune system can see and attack.  The virus is generally more destructive in the lytic phase as its destroying cells as it copies itself.

During the latent infection the virus is much less harmful but unfortunately it persists in the body able to become active at any moment.  The trouble with latency is that often during this stage the virus is only expressing a few proteins and the body does not notice them and allows the infected cells to persist.

If Vironyx new antibodies are specific for HIV latent proteins (whatever those happen to be??) than that would definitly be something to watch.  Even if it wasn't a total cure (ie couldn't recognize all latent cells), if the antibodies do a good job controlling the virus with far fewer side effects of current HAART meds, that would also be a big plus.

Let's watch and see what happens with the goats...

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