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Author Topic: peHRG214 - Clinical Trial in Texas  (Read 20494 times)

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Offline dario

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peHRG214 - Clinical Trial in Texas
« on: July 01, 2006, 07:11:20 AM »
A small company from New Zealand (see: http://www.virionyx.com) is to start phase II clinical trials of peHRG214 in October 2006.  (This is what Mr Simon Wilkonson told in an e-mail).

Personally I am bit sceptical of it.  The idea of passive immunotheraphy using polyclonal antibodies derived from goats seems a bit bizarre.  Nevertheless it apparently is getting fda approval.
... when I was young, I never needed anyone, making love was just for fun, those days are gone ... Eric Carmen (Raspberries)

Offline J220

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Re: peHRG214 - Clinical Trial in Texas
« Reply #1 on: July 01, 2006, 12:02:18 PM »
I was browsing their site, and their research to date looks good.

Can you imagine if this works all the way? That would be the kicks (no pun intended!), deriving the cure/ treatment from goats.

But hey, if it works it works, we'll gladly say baaaaaaahhhhhh al the way to to doctor's office to get the shots!

One thing that struck me from their research, some of the patients in the phase I trial experienced a significant rash...determined cause?

"...cell death, eg the destruction of large quantities of HIV virus and infected cells."

Sounds good to me!
« Last Edit: July 09, 2006, 01:13:33 PM by J220 »
"Hope is my philosophy
Just needs days in which to be
Love of Life means hope for me
Born on a New Day" - John David

Offline otherplaces

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Re: peHRG214 - Clinical Trial in Texas
« Reply #2 on: July 07, 2006, 01:38:43 AM »

Perhaps not as crazy as you think. From what I've read, prior to HIV retroviruses were primarily in the domain of animals...which is why the discovery of a retrovirus in humans was shocking and unexpected.

So to derive a therapy from animals who have already dealt with retroviruses longer than we have isn't so crazy.

brian


Offline ScienceGuy25

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Re: peHRG214 - Clinical Trial in Texas
« Reply #3 on: July 08, 2006, 10:30:25 PM »
Hey Guys

I work in the field of immunotherapy (working on my PhD). This idea is not at all far fetched.  In fact the current trend in antibody work is to develop the antibody in a mouse model and then "humanize" it so that the human immune system does not attack the antibody as foreign.

I'm not too familiar with their work but I would say it's one to watch and see.

Offline J220

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Re: peHRG214 - Clinical Trial in Texas
« Reply #4 on: July 09, 2006, 12:27:10 AM »
No question about it, this seems to have potential. In particular, from their website:

"Results also indicate that these [caprine] antibodies also destroy the infected human immune cells responsible for ongoing virus production within an infected human."

I am not sure but if I read this correctly this would mean latently-infected cells? I am going to write an email to see if that is what they mean.

Goats rule.
"Hope is my philosophy
Just needs days in which to be
Love of Life means hope for me
Born on a New Day" - John David

Offline dario

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Re: peHRG214 - Clinical Trial in Texas
« Reply #5 on: July 09, 2006, 06:02:22 AM »

Goats rule.

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!

... when I was young, I never needed anyone, making love was just for fun, those days are gone ... Eric Carmen (Raspberries)

Offline J220

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Re: peHRG214 - Clinical Trial in Texas
« Reply #6 on: July 09, 2006, 11:05:44 AM »
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 :)
"Hope is my philosophy
Just needs days in which to be
Love of Life means hope for me
Born on a New Day" - John David

Offline ScienceGuy25

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Re: peHRG214 - Clinical Trial in Texas
« Reply #7 on: July 09, 2006, 11:29:32 AM »
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.

Offline J220

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Re: peHRG214 - Clinical Trial in Texas
« Reply #8 on: July 09, 2006, 01:03:07 PM »
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.
« Last Edit: July 09, 2006, 01:06:35 PM by J220 »
"Hope is my philosophy
Just needs days in which to be
Love of Life means hope for me
Born on a New Day" - John David

Offline ScienceGuy25

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Re: peHRG214 - Clinical Trial in Texas
« Reply #9 on: July 09, 2006, 04:18:35 PM »
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...

Offline J220

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Re: peHRG214 - Clinical Trial in Texas
« Reply #10 on: July 09, 2006, 06:38:30 PM »
This is link for a poster that they produced for a conference last year. In it there is s table that shows the specific epitopes, and the proteins which reacted with the HRG214.

http://www.virionyx.com/pdf/2005/IAS%20Poster%20Jul05%20Rio.pdf

There is another poster that stated:

INTRODUCTION

1) PEHRG214 (HRG) is a polyclonal caprine IgG preparation produced by the immunization of goats with purified HIV proteins followed by booster immunization with synthetic peptides from highly conserved HIV epitope regions.

2) HRG antibodies react with at least seven unique epitope regions on HIV including two on gp120; and one each on gp41, p24, p66, p17, and p11.

3) HRG has been tested against laboratory strains and primary isolates from Clades A, B, and C. HIV infectivity was inhibited in all strains tested at HRG concentrations of 250 μg/mL or less.

4) In a single dose Phase I study HRG was well tolerated, and achieved adequate plasma concentrations. Median and maximum decreases in HIV-1 RNA levels at day 29 were 0.24 log10 and 2.2 log10, respectively.


I am not sure if this answers the queston of whether HRG recognizes latent-infected cells, but it certainly seems to indicate it!
"Hope is my philosophy
Just needs days in which to be
Love of Life means hope for me
Born on a New Day" - John David

Offline HIVworker

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Re: peHRG214 - Clinical Trial in Texas
« Reply #11 on: July 09, 2006, 11:10:06 PM »
It won't recognize latent infected cells because they don't express anything until activated. When activated, they can be killed either by HIV or CD8 cells. It's an interesting idea. However, I would like to see the evidence that they used goats for the reason Scienceguy suggested, as I think the answer might lie somewhere else and his ideas are incorrect conjecture.

R
« Last Edit: July 09, 2006, 11:13:22 PM by HIVworker »
NB. Any advice about HIV is given in addition to your own medical advice and not intended to replace it. You should never make clinical decisions based on what anyone says on the internet but rather check with your ID doctor first. Discussions from the internet are just that - Discussions. They may give you food for thought, but they should not direct you to do anything but fuel discussion.

Offline J220

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Re: peHRG214 - Clinical Trial in Texas
« Reply #12 on: July 09, 2006, 11:43:12 PM »
Hey Worker, what do you think they mean when they talk about 'disguise'? Isn't that what a latent-infected cell is doing, masquerading as a healthy cell? Also, can't there may be some type of expression that we don't know about, yet the HRG can and does recognize, thereby killing that infected cell? At least that is what I get from the virionyx website (www.virionyx.com).

"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. "

I am looking forward to a reply from New Zealand, when and if they do reply!

On another matter, it seems that Virionyx sold a part of their corporation to U.S. investors, with an eye on entering one of the U.S. stock exchanges (Nasdaq, I suppose, but you never know). I wouldn't mind putting some money in their stock, but it seems it will be at least a couple of years before they are listed.
"Hope is my philosophy
Just needs days in which to be
Love of Life means hope for me
Born on a New Day" - John David

Offline dario

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Re: peHRG214 - Clinical Trial in Texas
« Reply #13 on: July 10, 2006, 06:59:20 AM »
J220,
I think that "disguise" maybe means the ability of the virus to coat itself with sugars that makes it undetectable because the body would not be able to recognize it as a foreign organism.  I don't really think that "disguise"  means infected or dormant cells ... Perhaps I am wrong.

From the information found in the site of Virionyx, it seems that pehrg214 provokes also the lysis (self-destruction/death) of infected cells.  As you already said it would be interesting to see if latent cells are also targeted.  But again, if latent cells are targeted what percentage of them? And if just a little ammount of the bug keeps on circling around in the body would this be enough to infect enough T-cells that in turn become dormant? (It is the same old problem I've seen in other discussions ...)

IMHO the real novelty of this approach (i.e. using animal-derived antibodies) is avoiding the use of toxic drugs for those patients who tried all things available in the market.  Again this pehrg would not eradicate completely the bug but just keeps the viral load down, this time with something that is less-toxic than all the drugs that have been produced so far. 

... when I was young, I never needed anyone, making love was just for fun, those days are gone ... Eric Carmen (Raspberries)

Offline HIVworker

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Re: peHRG214 - Clinical Trial in Texas
« Reply #14 on: July 10, 2006, 07:49:33 AM »
Dario, you are not wrong. Your assessment of the use of the term 'disguise' in this context is completely correct. I would venture that the epitopes used are not just those that contain sugars but epitopes that are masked by the protein that are exposed when it undergoes the priming and fusion reactions. It's a trick a lot of viruses use to prevent the production of neutralizing antibodies.

R
NB. Any advice about HIV is given in addition to your own medical advice and not intended to replace it. You should never make clinical decisions based on what anyone says on the internet but rather check with your ID doctor first. Discussions from the internet are just that - Discussions. They may give you food for thought, but they should not direct you to do anything but fuel discussion.

Offline ScienceGuy25

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Re: peHRG214 - Clinical Trial in Texas
« Reply #15 on: July 10, 2006, 05:33:55 PM »
HIV Worker

I'm a little perturbed that you would simply dismiss my post as incorrect conjecture. I'm not sure what degrees you hold but i have a masters in biology and am working on a PhD in t-cell immunotherapy, broadly the field of molecular medicine.  I do not claim to be an HIV expert but I can certainly read and understand scientific literature.

http://www.aegis.org/pubs/aidswkly/1997/AW970601.html

This was some of the early work I saw citing the goat virus, which is why I suspected they tried to use goats as a model system in developing a goat polyclonal antibody.
 
My post about mouse technology  and humanizing antibodies is completely correct, you may or may not be familiar with the technology.

ScienceGuy

Offline J220

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Re: peHRG214 - Clinical Trial in Texas
« Reply #16 on: July 10, 2006, 08:20:23 PM »
Okay so I did receive a reply from someone from Virionyx, a very nice and helpful chap in a position to be familiar with their research, and even though I won't go into detals of what we discussed I will say that the research platform seems very, very good, to say the least, and in my opinion. A phase two trial is in the works and should start in the near future. I expect we should be hearing further info on this sometime next year, if all goes well. Fingers crossed, everybody!!
« Last Edit: July 10, 2006, 08:29:08 PM by J220 »
"Hope is my philosophy
Just needs days in which to be
Love of Life means hope for me
Born on a New Day" - John David

Offline HIVworker

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Re: peHRG214 - Clinical Trial in Texas
« Reply #17 on: July 10, 2006, 09:15:18 PM »
As I said, the part about the use of goats and that goat virus is mere conjecture on your part. They neither got the idea from the goat virus study nor did they do anything with goat viruses to make the antibodies for this treatment. The goat antibodies from the virus were for a vaccine that must have failed.

Quote
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. 

That link between the two was conjecture unless you have evidence from them suggesting otherwise. I don't think it is right because goats, sheep, cows, horses and donkeys are used in antibody production for other reasons than previous studies with viruses. Which is why I don't think that study, listed in 1997, is not relevant to the discussion.

R
« Last Edit: July 10, 2006, 09:22:43 PM by HIVworker »
NB. Any advice about HIV is given in addition to your own medical advice and not intended to replace it. You should never make clinical decisions based on what anyone says on the internet but rather check with your ID doctor first. Discussions from the internet are just that - Discussions. They may give you food for thought, but they should not direct you to do anything but fuel discussion.

Offline ScienceGuy25

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Re: peHRG214 - Clinical Trial in Texas
« Reply #18 on: July 10, 2006, 09:27:21 PM »
Where is your proof that the goat virus in no way factored into their decision to infect goats with HIV and monitor the anitbody response? Actually I found out some information about the guy who started Virionyx.  He was originally designing an antibody to an embryonic protein that is reactivated in certain forms of cancer. When searching databases of proteins that would bind his new antibody he noticed that HIV kept popping up.

The limited article I read said he chose to pursue the goat because of the better antibody response to HIV. It would not be at all unreasonable to assume that he had knowledge of this goat macrophage invading virus and the fact that goats mounted an effective immune response to it.

This what we call scientific reasoning based on previous data.  Just because something was published in 1997 doesn't make it irrelevant.  It adds to our working body of scientific knowlege. 

Take a step off your pedestal.  You nor I have all the answers.

Offline HIVworker

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Re: peHRG214 - Clinical Trial in Texas
« Reply #19 on: July 10, 2006, 09:36:58 PM »
The limited article I read said he chose to pursue the goat because of the better antibody response to HIV. It would not be at all unreasonable to assume that he had knowledge of this goat macrophage invading virus and the fact that goats mounted an effective immune response to it.

And that's conjecture. I noticed you toned it down from

 
Quote
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. 


to "not unreasonable to assume". I agree, it's not an unreasonable assumption but that is what it is - an assumption on your behalf. That 1997 study is still relevant to the goat virus - not at all to this study. Why make a big deal about it? Because you are reporting what you believe they did in a manner that indicates you know their motivations.

You are right, neither of us know what they did, but when you write a scientific review as you did -  don't be so dogmatic. Remember that when you write your Ph.D thesis.

R
NB. Any advice about HIV is given in addition to your own medical advice and not intended to replace it. You should never make clinical decisions based on what anyone says on the internet but rather check with your ID doctor first. Discussions from the internet are just that - Discussions. They may give you food for thought, but they should not direct you to do anything but fuel discussion.

Offline ScienceGuy25

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Re: peHRG214 - Clinical Trial in Texas
« Reply #20 on: July 10, 2006, 09:44:45 PM »
Their motivations, well let's see a big part is wanting to find an effective cure for HIV and a second party is monetary (of course)  - you can conjecture that all you want but i doubt this will be a free therapy ;)

Well lets look at the facts HIV worker.  The CAEV (caprine arthritis encephalitis virus) is a lentivirus and a distant cousin of HIV, known to infect goats and humans, and it is known that goats mount an effective immune response against this virus.

THEREFORE, if i'm VP of R&D the model organism i'm going to try first to make a new polyclonal antibody against HIV would be the goat rather than the much easier to work with, mouse or rat.

That my friend is science, so if you will, call it conjecture based on sound scientific reasoning.  I certainly hope your training would lead you to attack a problem such as this in a similar (efficient) manner.

Offline HIVworker

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Re: peHRG214 - Clinical Trial in Texas
« Reply #21 on: July 10, 2006, 10:06:16 PM »
You skirted the problem with your post again. You have gone from telling us what their motivations were for using the goat to trying to convince me that making antibodies against HIV is a good idea. Talk about trying to save your own argument.

My point has nothing to do with wanting to cure HIV as a 'motivation'. Tell me where you thought I said that and I'll show you where you got mixed up again.

If you need it spelling out, which you appear to do, the motivation I was talking about was going from this goat virus to making peptide-derived antibodies. If you have evidence to suggest your dogmatic statement about the reason they went from the virus to the peptide in goats is correct then state it. If not, then kindly stick to the evidence that you do know. The thread was started by someone asking about the antibody and you brought in some irrelevant data that you thought was relevant based on your own thoughts - which I have no problem with unless you state up front that this is why you believe (not know) that this is the case. Otherwise you are providing incorrect evidence for the motivation to choose goats as a host for the antibodies. It sounds like a cooky idea but the motivation they had for choosing the goat probably doesn't lie where you suggested (got the idea from viruses) but more likely due to the fact that goats have been used as antibody factories by the bioscience industry for years - a fact you have only just now hit on. Likewise the horse and donkey.

Therefore the whole bit about viruses, while interesting, has no bearing on the idea to choose the goat for this particular line of therapy in the first place. It is my 'conjecture' that they chose the goat as an antibody factory because they are commonly used as such and they have goats from previous studies and know how to handle them. The stuff about viruses has no bearing on it.

R
« Last Edit: July 10, 2006, 10:11:01 PM by HIVworker »
NB. Any advice about HIV is given in addition to your own medical advice and not intended to replace it. You should never make clinical decisions based on what anyone says on the internet but rather check with your ID doctor first. Discussions from the internet are just that - Discussions. They may give you food for thought, but they should not direct you to do anything but fuel discussion.

Offline ScienceGuy25

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Re: peHRG214 - Clinical Trial in Texas
« Reply #22 on: July 10, 2006, 10:27:13 PM »
HIV Worker

You don't believe they had knowledge of this goat virus and that it didn't factor into their decision, that is your opinion which you are definitly entitled too, but have no evidence to support. I also think  your view is quite naive for the following.  First, i'm fairly sure the rabbit is the most common animal used for making polyclonal antibodies, so why not choose it? (smaller, cheaper to maintain).  Why not the donkey? (if you need a large animal)

 The decision to use an extremely expensive animal model like a goat obviously required extensive research, you don't think the goat virus came up at all in that research????  I don't know how much you know about large animal models but they're not just laying around pumping out antibodies at will, it's a huge undertaking to use such an animal.  No one would make that kind of investment without some sort of background knowlege on why they thought goats would produce effective polyclonal antibodies against unique HIV epitopes.  It wasn't simply a serendipitous discovery.

Anyhow, I thought i did give the impression that i wasn't certain about their reasoning but maybe I didn't make that clear.  Nevertheless I don't believe you're right and I'm willing to bet they were aware of the literature describing these effective anitbodies to the goat virus. It may not have been their sole decision but seems more logical than not that it played a part.

Anyways this discussion is rather irrelevant to anyone besides us so lets leave at reasonable scientific disagreement. (or maybe i'll try to find out next time I'm in New Zealand for a scientific meeting ;)

Offline ScienceGuy25

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Re: peHRG214 - Clinical Trial in Texas
« Reply #23 on: July 10, 2006, 10:31:22 PM »
Couldn't resist, one last comment.  Goat, rabbit, donkey antibodies etc. are made by injecting a human antigen into the animal and then isolating the antibodies the animal makes against the human antigen.  These types of antibodies are used in scientfic research for detecting that "antigen" or protein in the work that we do.  Those antibodies however cannot be simply injected into a human as they're are of non-human origin.

So really it's kind of irrelevant how many years you've been making antibodies with rabbits and goats unless you have new technologies to "humanize" those antibodies.

OK I'll stop with the science debate now ;)

Offline HIVworker

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Re: peHRG214 - Clinical Trial in Texas
« Reply #24 on: July 10, 2006, 10:32:43 PM »
Goats are frequently used as antibody factories. You never done a western, RIA or FACS then....

Goats are common large scale antibody factories, you can buy them from almost all of the major supply companies.

Yes, I have no evidence for my reasoning. Neither do you, which is why I called you out on being dogmatic.

T H E   E N D

R
NB. Any advice about HIV is given in addition to your own medical advice and not intended to replace it. You should never make clinical decisions based on what anyone says on the internet but rather check with your ID doctor first. Discussions from the internet are just that - Discussions. They may give you food for thought, but they should not direct you to do anything but fuel discussion.

Offline ScienceGuy25

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Re: peHRG214 - Clinical Trial in Texas
« Reply #25 on: July 10, 2006, 10:33:40 PM »
Do all 3, in my sleep ;)

Offline HIVworker

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Re: peHRG214 - Clinical Trial in Texas
« Reply #26 on: July 10, 2006, 10:34:04 PM »
Do all 3, in my sleep ;)

Then wake up and do them correctly.

R
NB. Any advice about HIV is given in addition to your own medical advice and not intended to replace it. You should never make clinical decisions based on what anyone says on the internet but rather check with your ID doctor first. Discussions from the internet are just that - Discussions. They may give you food for thought, but they should not direct you to do anything but fuel discussion.

Offline HIVworker

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Re: peHRG214 - Clinical Trial in Texas
« Reply #27 on: July 10, 2006, 10:36:05 PM »
Couldn't resist, one last comment.  Goat, rabbit, donkey antibodies etc. are made by injecting a human antigen into the animal and then isolating the antibodies the animal makes against the human antigen.  These types of antibodies are used in scientfic research for detecting that "antigen" or protein in the work that we do.  Those antibodies however cannot be simply injected into a human as they're are of non-human origin.

So really it's kind of irrelevant how many years you've been making antibodies with rabbits and goats unless you have new technologies to "humanize" those antibodies.

OK I'll stop with the science debate now ;)

So that is the real reason they used goats then - not this virus crap that you came up with......thanks for that. Yes stop with the science 'debate' as you seem to be missing the point...
NB. Any advice about HIV is given in addition to your own medical advice and not intended to replace it. You should never make clinical decisions based on what anyone says on the internet but rather check with your ID doctor first. Discussions from the internet are just that - Discussions. They may give you food for thought, but they should not direct you to do anything but fuel discussion.

Offline ScienceGuy25

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Re: peHRG214 - Clinical Trial in Texas
« Reply #28 on: July 10, 2006, 10:38:04 PM »
Lol, you are quite hard headed, is it because you work in the field and were not aware of this goat virus, is that why you're so admant against it........???

Its quite hard to believe you can deny such an obvious conclusion.  We use orthologous genes, proteins etc. all time in biomedicine, you don't think we'd investigate an orthologous virus?

Offline HIVworker

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Re: peHRG214 - Clinical Trial in Texas
« Reply #29 on: July 10, 2006, 10:39:40 PM »
No I am hard headed about it because you made an incorrect leap of faith when explaining it to someone who didn't know anything about it.

If it makes you feel better to think that it has somehow got something to do with scientific jealousy, then you are welcome to that conjecture too.

R
NB. Any advice about HIV is given in addition to your own medical advice and not intended to replace it. You should never make clinical decisions based on what anyone says on the internet but rather check with your ID doctor first. Discussions from the internet are just that - Discussions. They may give you food for thought, but they should not direct you to do anything but fuel discussion.

Offline ScienceGuy25

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Re: peHRG214 - Clinical Trial in Texas
« Reply #30 on: July 10, 2006, 10:39:59 PM »
Actually the antibody humanization technology is much more advanced in mice because of our advanced genetics in mice.  So under your logic they should be using mice. 

However it's most likely they used goats because of the effective antibody response goats make to a lentiviral cousin of HIV ;)

Offline ScienceGuy25

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Re: peHRG214 - Clinical Trial in Texas
« Reply #31 on: July 10, 2006, 10:41:41 PM »
I will admit fault in that maybe i didn't make it clear enough that it was just my professional opinion.  Nonetheless I think I provided that person with the most reasonable, most scientifically valid opinion thus far. 

Offline HIVworker

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Re: peHRG214 - Clinical Trial in Texas
« Reply #32 on: July 10, 2006, 10:41:59 PM »
Good lad! you used the term "Likely"

You made me proud!

R
NB. Any advice about HIV is given in addition to your own medical advice and not intended to replace it. You should never make clinical decisions based on what anyone says on the internet but rather check with your ID doctor first. Discussions from the internet are just that - Discussions. They may give you food for thought, but they should not direct you to do anything but fuel discussion.

Offline HIVworker

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Re: peHRG214 - Clinical Trial in Texas
« Reply #33 on: July 10, 2006, 10:42:47 PM »
I will admit fault in that maybe i didn't make it clear enough that it was just my professional opinion.  Nonetheless I think I provided that person with the most reasonable, most scientifically valid opinion thus far. 

Good boy.
NB. Any advice about HIV is given in addition to your own medical advice and not intended to replace it. You should never make clinical decisions based on what anyone says on the internet but rather check with your ID doctor first. Discussions from the internet are just that - Discussions. They may give you food for thought, but they should not direct you to do anything but fuel discussion.

Offline ScienceGuy25

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Re: peHRG214 - Clinical Trial in Texas
« Reply #34 on: July 10, 2006, 10:53:55 PM »
Are you being condescending because a young gun has showed you up a little bit?  Really we should be working together to provide the most accurate and scentifically sound ideas...

You're never too old to stop learning HIV Worker, especially when you're in this field.  BTW I've taught several science courses everything from human anatomy/physiology to molecular genetics, several of my students were close to twice my age (one great old guy probably close to 3X) ;)

Offline HIVworker

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Re: peHRG214 - Clinical Trial in Texas
« Reply #35 on: July 10, 2006, 11:12:42 PM »
I'm so pleased you feel the need to constantly tell me how good you are. But from what you have written it seems that you are still wet behind the ears enough to not know why you were wrong or how to correct yourself. But rather keep coming with the "I do assays in my sleep, I taught people in their 30s, I am doing a Ph.D". Who you trying to convince? Us or you?

You haven't shown me up at all. You merely got caught out making an incorrect leap of faith and all your attempts to cover it up have demonstrated that you didn't understand the problem with your incorrect post nor had the balls to fess up that you jumped the gun - but instead come out like a typical PhD student and convince everyone you are great. I don't mind being wrong, I do mind people who don't admit it. Your post on viruses had nothing to do with the antibody study and any attempts to link it to this study were complete conjecture.

R
NB. Any advice about HIV is given in addition to your own medical advice and not intended to replace it. You should never make clinical decisions based on what anyone says on the internet but rather check with your ID doctor first. Discussions from the internet are just that - Discussions. They may give you food for thought, but they should not direct you to do anything but fuel discussion.

Offline ScienceGuy25

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Re: peHRG214 - Clinical Trial in Texas
« Reply #36 on: July 10, 2006, 11:38:41 PM »

You haven't shown me up at all. You merely got caught out making an incorrect leap of faith and all your attempts to cover it up have demonstrated that you didn't understand the problem with your incorrect post nor had the balls to fess up that you jumped the gun - but instead come out like a typical PhD student and convince everyone you are great. I don't mind being wrong, I do mind people who don't admit it. Your post on viruses had nothing to do with the antibody study and any attempts to link it to this study were complete conjecture.

R

You keep saying that my post on the virus is incorrect and you have absolutely no proof to support that.  I dont know where you went to school but it is beyond me that you can't see the logical connection.  You have not shown a very advanced understanding of new antibody technology, rather you wish for us to accept what you say as the truth based on your age???  What was your degree again?...Like a typical  aging technician you seem to hold a grudge against the PhD student.  (ok - that was probably not called for but u started it ;)

I have not tried to cover anything up.  Rather i prevented sound scientific reasoning why i believe i'm right. You on the other hand have provided no evidence as to why you're assumption is correct.  Again i still can't believe someone working in HIV antibody research wouldn't take into account the goat lentivirus studies.  If they didn't I would call it bad science on there part and suggest they increase their background knowlege!

Offline HIVworker

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Re: peHRG214 - Clinical Trial in Texas
« Reply #37 on: July 10, 2006, 11:51:21 PM »
Here, once again, is the point I take issue with...

Quote
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.

That indicates that they looked at their virus and made a decision to go to make antibodies in the goat against HIV. A complete leap of faith on your behalf. It's not that I disagree that they could of thought that - I've actually never said that. It's just you state it as a fact...as if YOU had the evidence that you somehow are asking me for. It's ironic that you end your twisted argument by saying I have no proof that they didn't. I of course do not. However, you dogmatically stated they did. So I wanted to see the evidence, rather than taking your rather arrogant supposition at face value. Its not up to me to prove they didn't. You stated it as a fact, it is up to you to prove they did. So go ahead and do so.

You know, science and show me the data and all. So forget trying to impress everyone with your credentials, forget trying to belittle me with your comments that show your age and maturity. But retract everything you said about the virus as your personal supposition until you gain evidence that it is true. It's a board that deals in facts and not what you personally have googled in an attempt to explain why they use goats, likely as they may or may not be.

A question was asked and you provided a lot of their old data. It is up to you to prove it has any relevance to the question asked.

R.

Technician. I like that :)
« Last Edit: July 10, 2006, 11:54:04 PM by HIVworker »
NB. Any advice about HIV is given in addition to your own medical advice and not intended to replace it. You should never make clinical decisions based on what anyone says on the internet but rather check with your ID doctor first. Discussions from the internet are just that - Discussions. They may give you food for thought, but they should not direct you to do anything but fuel discussion.

Offline ScienceGuy25

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Re: peHRG214 - Clinical Trial in Texas
« Reply #38 on: July 11, 2006, 12:04:30 AM »
At least we're getting somewhere. Again I admit I overstated that and should have put that it was my suspicion.  Since this debate is totally useless I say we put it to rest for good.  It's somewhat comical if you look at what we've wasted all this time debating over - the reasons for using goats to develop polyclonal antibodies.  The big test will come when the phase 2 results are in.

BTW i wasn't trying to impress people with my credentials...when i talked about teaching classes i was trying to make a witty reference to the fact that i was "schooling" you on new antibody technology.  LoL :P

That was fun anyways - but enough of the bickering i think both you and I could do some good here if we let this thread die.

Good night.

Offline HIVworker

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Re: peHRG214 - Clinical Trial in Texas
« Reply #39 on: July 11, 2006, 12:07:31 AM »
Well, I am going to bed.

For anyone who is interested about a possible reason they started this study, you can read it below. I'll give anyone $500 if they spot a goat virus infecting monocytes and macrophages as having anything to do with it.

Quote
Back in the early 1990s, American-born Gelder was studying the subtle changes that occur in cancer cells. Specifically, he was looking at the sequence of a protein that is active in embryos, turns off just before birth and is re-expressed in certain forms of cancer. One thing led to another, and before long he’d produced antibodies to the protein.

Then, as often happens in scientific research, serendipity kicked in. When he looked at other human protein databases that fit the antibodies, HIV kept popping up as a match. He sent the antibodies to a colleague at Baylor College of Medicine who determined that the antibodies did, in fact, react with HIV.

“We didn’t know exactly at what point we had inhibited HIV activity,” says Gelder. “But it evolved into the hypothesis that maybe HIV avoids immune detection by antigenic mimicry.” In other words, the virus tricks the body into thinking it’s not foreign.

Thus was born the prosaically named HRG214, the compound that Gelder hopes will one day be a treatment for AIDS. These days Gelder is based in Auckland, and the vehicle for the HRG214 research programme is New Zealand company Virionyx — of which he is lead scientist, primary shareholder and a director.

Or it could be as scienceguy said...

Quote
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.

I'll consider myself schooled in your brand of conjecture...
NB. Any advice about HIV is given in addition to your own medical advice and not intended to replace it. You should never make clinical decisions based on what anyone says on the internet but rather check with your ID doctor first. Discussions from the internet are just that - Discussions. They may give you food for thought, but they should not direct you to do anything but fuel discussion.

Offline ScienceGuy25

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Re: peHRG214 - Clinical Trial in Texas
« Reply #40 on: July 11, 2006, 12:10:44 AM »
And i'll relish the fact that you'll be educating yourself on how antibodies are humanized ;)

Offline J220

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Re: peHRG214 - Clinical Trial in Texas
« Reply #41 on: July 11, 2006, 12:17:24 AM »
Well as I said, I am fortunate to be corresponding with someone from Virionyx, and his last email included a comment about this debate (I had sent him the link and invited him to browse), so I am glad you guys are cooling off and keeping it civil and to the point...I really like these kinds of debates but it is dissapointing when it gets too personal, so thank you both for keeping it professional.
« Last Edit: July 11, 2006, 01:12:52 AM by J220 »
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Offline Matty the Damned

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Re: peHRG214 - Clinical Trial in Texas
« Reply #42 on: July 11, 2006, 12:19:37 AM »
ScienceGuy,

Give up now. You're getting creamed babe. It's sickening to watch.

MtD
(Who has seen people tangle with HIVworker before -- it's never pretty)

Offline lydgate

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Re: peHRG214 - Clinical Trial in Texas
« Reply #43 on: July 11, 2006, 12:27:39 AM »
Enough already. This is turning into a scientific version of Krystle and Alexis on "Dynasty."
Her finely-touched spirit had still its fine issues, though they were not widely visible. Her full nature, like that river of which Cyrus broke the strength, spent itself in channels which had no great name on the earth. But the effect of her being on those around her was incalculably diffusive: for the growing good of the world is partly dependent on unhistoric acts; and that things are not so ill with you and me as they might have been, is half owing to the number who lived faithfully a hidden life, and rest in unvisited tombs.

George Eliot, Middlemarch, final paragraph

Offline HIVworker

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Re: peHRG214 - Clinical Trial in Texas
« Reply #44 on: July 11, 2006, 07:05:29 AM »
And I'll relish the fact that you'll be educating yourself on how antibodies are humanized ;)

As I said before, it's got nothing to do with that and it never has. Stop trying to 'win' something out of this and PLEASE be mature enough to see the bigger picture here.'

I'm making a serious point about writing a review article on science and you keep dragging it back to the fact that you are a PhD student, have taught people 3x your age or implying by transparent innuendo that you know more about this than some people. You THINK I am debating the facts of things I am not - dragging the argument back to where you are right and not to where you were wrong. I've never said the actual data was wrong and the fact you defended it so adamantly suggests you either thought I did or are insecure in some way.

It's about writing a review. Nothing more. Never has been anything more. It's about backing up your statements with data and evidence. A good scientist would have taken that criticism on the chin and gone looking for evidence - contacted the company. I gave you ample opportunity to do so. You chose not to do that but instead embark on a personal campaign on how you knew best. THAT is what you need to work on. Not understanding data because any scientist can do that, its about reporting what you found. I gave you an opportunity to find out for us, instead J220 did for us. You could have rammed my comment down my throat in being a good scientist and supplying evidence to back up your conviction. You did not. As others said, you got creamed and it frustrates me that someone with your intelligence allowed that to happen. You could have just accepted the criticism and provided evidence. That's what you do when you write research articles - you don't go round putting down how clever you are - you just supply evidence.

It's not about what I or you know, its about reporting what we DO know. As you so rightly point out - we don't know. When we don't know something we put down that we don't and SUPPOSE that they made the logical leap of faith. In the absence of knowing whether they did or not that's all we've got. People look to us as scientists for reasons why scientific studies are conducted where they are and in the interests of being correct, I called you out on it. Why is it that Matty can see it and you can't?

So be a good scientist and find the data. And rejoice in when you find out you are right. If you are I will champion that with you, but at least go find out what was right about WHY they use goats in the first place and not dogmatically claim something when you don't know it to be true.

R
« Last Edit: July 11, 2006, 07:41:35 AM by HIVworker »
NB. Any advice about HIV is given in addition to your own medical advice and not intended to replace it. You should never make clinical decisions based on what anyone says on the internet but rather check with your ID doctor first. Discussions from the internet are just that - Discussions. They may give you food for thought, but they should not direct you to do anything but fuel discussion.

Offline dario

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Re: peHRG214 - Clinical Trial in Texas
« Reply #45 on: July 11, 2006, 07:44:50 AM »
Mamma mia!  It looks like Zidane vs Materazzi ...

I forgot why I started this thread!  Anyway, I have other questions:  Was this approach tried in the past to target other bugs? To be more specific, are there any other diseases that are currently "cured" or "kept under control" by animal-derived antibodies? If this pehrg proves to be effective against Hiv, does it clear all latent infected cells?
... when I was young, I never needed anyone, making love was just for fun, those days are gone ... Eric Carmen (Raspberries)

Offline ScienceGuy25

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Re: peHRG214 - Clinical Trial in Texas
« Reply #46 on: July 11, 2006, 09:12:22 AM »
All right i'm officially ending this.  I agree with you, the way i wrote that original post was wrong.  I feel that you blew that overstatement slightly out of proportion in terms of any real harm it did.  But, reading it again I really don't know why I worded it the way I did as i'm generally careful not to overstate my thought process.

Nonetheless, the whole point is really rather moot and highly unsignificant to most people reading this thread.  I would off this conjecture, most people here could really careless whether the antibodies come from goat, dog, cat or alien if they provide a new benefit in the fight against HIV.

But alas, my original post should have read I suspect that buidling off of earlier work with the CAE virus, Virionyx chose the goat as a model system to produce their new therapy.  As HIV worker points out this may not have been the reason for their decision.  Working in the field they were undoubtedly aware of this virus but it may not have played into their reasoning for using the goats.

I suggest we move on now...

Offline ScienceGuy25

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Re: peHRG214 - Clinical Trial in Texas
« Reply #47 on: July 11, 2006, 09:26:25 AM »
Mamma mia!  It looks like Zidane vs Materazzi ...

I forgot why I started this thread!  Anyway, I have other questions:  Was this approach tried in the past to target other bugs? To be more specific, are there any other diseases that are currently "cured" or "kept under control" by animal-derived antibodies? If this pehrg proves to be effective against Hiv, does it clear all latent infected cells?


Thanks for helping to change the direction of that pointless thread ;)  Actually Dario there are some successes with antibodies.  I'm more familiar with oncology (cancer) so I can give you two of the prime examples I know about in those fields.  There's an antibody called Herceptin (traztuzimab) which targets the overexpressied HER2 protein on some breast cancer cells.  This therapy has so far proven to be very effective for some patients with breast cancer - patients will often take this drug in combination with significantly lower amounts of chemotherapy so that their side effects are much less.  There's also an antibody called rituximab which targets a molecule known as CD20 on B-cell lymphomas. 

I can't think of any man made  antibodies to viruses off the top of my head.  Nonetheless the technology is similar between fighting a cancer and fighting a virus.  It's all dependent on making an antibody which is specific to some protein antigen(s) that is abberantly expressed on an infected cell. Once the antibody binds they can can kill the target cells through things like complement and natural killer cells.

 I know there has been a lot of work  investigating antibodies for the bird flu. Maybe someone knows something more specific about man made antiviral antibodies...

Offline HIVworker

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Re: peHRG214 - Clinical Trial in Texas
« Reply #48 on: July 11, 2006, 09:48:26 AM »
Dario,

My apologies for the hijack of your thread. To remind you...you said you were skeptical of the use of polyclonal antibodies derived from animals and wanted to know more. It seems that the creators of this therapy stumbled on it from another line of research - that of antibodies to cancer cells. They asked a research group to monitor the infectivity of HIV in the presence of this antibody and found that they were broadly neutralizing. Given this data they sought to increase the broad-range of antibodies to HIV by injecting goats with peptides and purified protein from HIV. In my opinion the reason they used goats was three fold.

Firstly it is a matter of simple production. Antibodies are very hard to make in large quantities and so you need a big animal that you can repeatidly bleed. It's a common approach in antibody therapy to use large animals and a rabbit, mouse or other small mammal wouldn't produce the quantity required for a human trial. Other human trials with neutralizing antibodies such as 2F5 used gram quantities of antibody (which is a vast amount). However, although the antibodies were broadly neutralizing in vitro, they had little effect in vivo - resulting in no ability to maintain low viral load after viral load was knock-down with HAART therapy. Ultimately they failed because the antibodies were cleared VERY quickly by the human body and weren't around long enough to elicit an effect. Some argued that this was the end of the therapeutic antibody idea. I don't share that view.

Secondly they had experience with goat antibodies to their cancer cells. So with all protocols in place they likely chose to see if they could increase their neutralizing potential by using the same animal that they used before.

Thirdly goats appeared to produce antibodies that were more neutralizing from their previous cancer study - so it makes sense to stick with what you know.


The human body raises antibodies to the fusion protein of HIV (termed the envelope protein or Env) but normally these don't have any neutralizing effect. HIV hides the guts of the fusion machine until right when it is going to use it and you can effectively coat the virus with the antibodies made during acute infection and they don't stop it getting into the cell. So a different approach was needed. What companies like Virionxy have done is inject peptides (small pieces of the fusion protein) into goats in an attempt to produce antibodies to parts of the protein that are normally hidden. I believe this is why they used peptides in their study. It is likely they did what other companies have done and not find which peptide was important but rather inject a whole bunch of them and let nature pick which was best. Given the broad neutralizing antisera they then have to humanize them so the body doesn't clear them so quickly. The human body will recognize something that isn't human and raise antibodies to it....effectively getting rid of the thing trying to help it.

As to your question about latent cells. Here is what I think. Latent cells contain the HIV provirus integrated into a silent area of the human genome. It sits their quietly not making any protein. Therefore to the body there is nothing wrong with this cell as the human body would only recognize it as not-human if it were making HIV proteins. All available evidence suggests they don't. So in the absence of a 'flag' for the body to recognize the latent cells, neither the body nor the antibody will do anything to that cell.

R
NB. Any advice about HIV is given in addition to your own medical advice and not intended to replace it. You should never make clinical decisions based on what anyone says on the internet but rather check with your ID doctor first. Discussions from the internet are just that - Discussions. They may give you food for thought, but they should not direct you to do anything but fuel discussion.

Offline HIVworker

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Re: peHRG214 - Clinical Trial in Texas
« Reply #49 on: July 11, 2006, 09:49:23 AM »
All right i'm officially ending this.  I agree with you, the way i wrote that original post was wrong.  I feel that you blew that overstatement slightly out of proportion in terms of any real harm it did.  But, reading it again I really don't know why I worded it the way I did as i'm generally careful not to overstate my thought process.

Nonetheless, the whole point is really rather moot and highly unsignificant to most people reading this thread.  I would off this conjecture, most people here could really careless whether the antibodies come from goat, dog, cat or alien if they provide a new benefit in the fight against HIV.

But alas, my original post should have read I suspect that buidling off of earlier work with the CAE virus, Virionyx chose the goat as a model system to produce their new therapy.  As HIV worker points out this may not have been the reason for their decision.  Working in the field they were undoubtedly aware of this virus but it may not have played into their reasoning for using the goats.

I suggest we move on now...

Good, if you said that 20 posts ago you could have avoided all of this.
NB. Any advice about HIV is given in addition to your own medical advice and not intended to replace it. You should never make clinical decisions based on what anyone says on the internet but rather check with your ID doctor first. Discussions from the internet are just that - Discussions. They may give you food for thought, but they should not direct you to do anything but fuel discussion.

 


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