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Author Topic: Could this be the holy grail ?  (Read 150513 times)

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Offline veritas

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Re: Could this be the holy grail ?
« Reply #50 on: December 09, 2008, 01:26:00 PM »


UK reports about Bavituximab:


http://drugdiscoveryopinion.com/

Offline veritas

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Offline leit

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Re: Could this be the holy grail ?
« Reply #52 on: December 14, 2008, 12:12:14 PM »
It attacks the exposed phosphalipid attached to the virion and also to the reservoir cell that the virus has infected.

Hi "veritas"!

To your knowledge, is there any scientific paper showing indisputably that also the resting cells of the reservoirs, which are in a unique condition, have their PS exposed? This is crucial, I think.
Thank you!


Offline veritas

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Re: Could this be the holy grail ?
« Reply #53 on: December 14, 2008, 06:42:31 PM »

leit,

Please read the above " HIV - Phosphatidylserine Breakthrough " with references. In a word "yes". All cells invaded by the virus flip ps jnside out. So yes anti-ps should be able to go after resting cells. The trick is to generate the appropriate dosage to get them all. Anti-ps seems to teach the immune system
how to do this on its own (adaptive immunity). Your immune system goes everywhere. I believe if you read the entire thread your questions will be answered.

veritas

Offline veritas

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Re: Could this be the holy grail ?
« Reply #54 on: December 15, 2008, 05:17:04 AM »

leit,

Here's some backup research ----- not an easy read:


  http://www.jacionline.org/article/PIIS0091674908007252/fulltext


veritas

Offline veritas

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Re: Could this be the holy grail ?
« Reply #55 on: December 18, 2008, 12:58:45 PM »

Offline veritas

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Re: Could this be the holy grail ?
« Reply #56 on: January 06, 2009, 04:50:00 AM »

Offline veritas

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Offline veritas

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Re: Could this be the holy grail ?
« Reply #58 on: January 06, 2009, 08:15:09 AM »

For those of you who want to know more about Bavituximab that is presently in clinical trials for co-infection hepc and hiv and being studied at CHAVI at Duke University  (anti-ps) for both a therapeutic and vaccine please read:


http://www.peregrineinc.com/images/stories/media/siteFiles/20081121_BavituximabAV.pdf

Offline hotpuppy

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Re: Could this be the holy grail ?
« Reply #59 on: January 06, 2009, 11:34:19 PM »
I have no interest in reading 97 pages of a .pdf file, but thanks.  I'll leave that to someone else here to do.


I have to agree.  This  type of post is annoying when there is just a link and a sensational subject.  It would be really NICE if people posted a short 2 or 3 sentence summary of the link.  That way I can decide if it is worth going and reading.

As a general rule, patent applications read like federal law.  Great for insomnia.
Don't obsess over the wrong things.  Life isn't about your numbers, it isn't about this forum, it isn't about someone's opinion.  It's about getting out there and enjoying it.   I am a person with HIV - not the other way around.

Offline veritas

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Re: Could this be the holy grail ?
« Reply #60 on: January 07, 2009, 09:25:53 AM »

hotpuppy,

This thread is dedicated to anti-ps therapy as it is progressing through the research stage and clinical trials. I realise that the science is difficult to understand and many of the studies herein are an effort to read without background info needed to understand their significance, however, by opening the links and reading both the heading and perhaps the first few sentences should give you an indication as to their content and you can then make a decision to read or not. Some readers don't want to follow the science this closely and I can appreciate that, however there are readers of this thread who do want to know what the status of the science is and believe as I do that anti-ps is  very promising. The "sensational headings" as you call them make sense if you read the link and have been following the thread and understand the moa (method of action ) of the antibody. I tried to explain the moa in an earlier post to Miss philicia. If you have any questions regarding the science I will try to answer however, everyone has to make up their own minds as to the merit of the science and the links. It is your decision to read or not to read.

veritas

Offline hotpuppy

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Re: Could this be the holy grail ?
« Reply #61 on: January 07, 2009, 12:17:29 PM »
I'm just suggesting that you will share information with more people if you do more than post a link.

Posting an enticing headline with a link constitues a tease online.  It annoys most internet users.  It's the online equivalent of having a candy bar wrapper, nicely sealed, that says "yummy treat inside" and when you open it, all that is inside is a coupon and directions to a local store.  It would piss you off.  It's a broken expectation.

The thread should be titled: Anti-PS Therapy update

It's sensationalist to call anything a holy grail.  But you call it what you want.  It simply discredits you as a reliable source when you set and break expectations.

an example of what I'm suggesting is:

"link here"

I found an article about (what), that is important because (why), and is an exciting update (your reason).

That gives someone who clicks on the thread an idea of what you found and makes you helpful.

The science is really not that difficult to understand.  The summary is really easy, here I'll do one:

Researchers are targeting a chemical called Phosphatidylserine (PS).  PS normally occurs inside the cell, however in virus infected cells it shows up on the outside of the cell.  Reserachers think that they can leverage this with new treatments that target PS, and thus the virus infected cells.  Researchers believe that they can get to latent reservoirs using this technique.


**** Next link
  http://www.jacionline.org/article/PIIS0091674908007252/fulltext

This link covers basic HIV-1 immunology and vaccine background theory.  Of particular interest are the infection timeline which clearly shows why early intervention and treatment are advantageous.  It gives a theorized timeline for when latent cells are formed in one graph.

Another paragraph in this article discusses the link between cd4 depletion and progression to AIDS.  Interesting reading if you are interested in vaccine development or background HIV theory.

*** end example.

Not that hard and shows respect for others like Ms. Phillicia who may not want or have time to read everything.  It gives her enough information to make an informed decision about whether they want to read someone's doctoral power point http://www3.niaid.nih.gov/Biodefense/PDF/tarvacin.pdf (very cheesy graphics and clearly a justification presentation).

The easier you make it for others to understand what you are sharing, the more people will appreciate it. 
Don't obsess over the wrong things.  Life isn't about your numbers, it isn't about this forum, it isn't about someone's opinion.  It's about getting out there and enjoying it.   I am a person with HIV - not the other way around.

Offline veritas

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Re: Could this be the holy grail ?
« Reply #62 on: January 07, 2009, 12:57:10 PM »
hotpuppy,

I'll give you an example of not fully under standing the moa of the antibody and its potential implications: That simplistic powerpoint with the "chessy graphics" that you referred to was presented to the Dept of Defense for their biological threat initiative. The presentation earned the company developing this therapy a 44million dollar contract for further development in conjunction with the dept of defense.

I also see that you were able to quickly read the links and get the jist of the information. If you can do it then shouldn't others be able ito do the same?
By the way, I purposely used the Holy Grail analogy with the "Could "proviso because should the antibody prove to work in humans as it did in preclinicals then we have a cure and a vaccine. That would be the HOLY GRAIL! 

veritas

Offline georgep77

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Re: Could this be the holy grail ?
« Reply #63 on: January 07, 2009, 05:02:31 PM »
I completely agree with you veritas, thanks for your research news....

                                              :D
Come on Sangamo,  Geovax,  Bionor immuno, ...Make us happy !!!
+ 2008

Offline hotpuppy

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Re: Could this be the holy grail ?
« Reply #64 on: January 07, 2009, 11:31:36 PM »
I also see that you were able to quickly read the links and get the jist of the information. If you can do it then shouldn't others be able ito do the same?
By the way, I purposely used the Holy Grail analogy with the "Could "proviso because should the antibody prove to work in humans as it did in preclinicals then we have a cure and a vaccine. That would be the HOLY GRAIL! 

1.  You can continue to post a link only.  I'm just pointing out that you will be useful to alot more people when you post some information about the link.  Being narrowminded and rude is your right.  Just remember not everyone has a good internet link, a good computer, or the time to wade through research.

2. Just because you and I are capable of reading through collegiate and scientific research does not mean that others on here are.  Locking them out is wrong.  The goal of the forums is to help others and a big part of helping is sharing knowledge in a format that makes it accessible to others.

3. I think it's sensationalist to call something a holy grail or cure.  The papers you linked to clearly indicate that there are substantial and real obstacles.  Anti-PS and monoclonal AB are two paths that researchers are evaluating.  Four years ago we were "assured" that an effective vaccine was just around the corner.  In 1985 (or maybe 83) the CDC promised us a vaccine in 2 years.  (See PBS Frontline 2006 AIDS History - paraphrased title - 2 hour DVD program on AIDS History). 

4. While you may think otherwise, 44 million doesn't go far in research.  Especially government funded research.  I still think it's a

5. If you want a functional vaccine.... we already have the resources.  http://www.medpagetoday.com/MeetingCoverage/ICAAC/6719  Dr. Jacobson states what I suspected.  Entry inhibitors can provide an effective barrier to R5 infection.  This would stop, at a minimum, 60 to 70% of the infections.  Probably not cheap, probably not as convenient as a shot, but a definate, viable option with few side affects.  When it comes to treatments, I'm afraid that a pill is going to win out over anything that looks like a genetically engineered treatment... at least in the short term.  The only problem is that it isn't a classical vaccine, and we are not likely to succeed with a classical vaccine. 

Don't obsess over the wrong things.  Life isn't about your numbers, it isn't about this forum, it isn't about someone's opinion.  It's about getting out there and enjoying it.   I am a person with HIV - not the other way around.

Offline veritas

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Re: Could this be the holy grail ?
« Reply #65 on: January 08, 2009, 05:46:56 AM »

Hotpuppy,

I suggest you do more research into PRO140. You will find that the antibody must  be redosed perpetually to keep the virus ud and does nothing for the hidden or latent cells. Anti-ps will not only eliminate free-flowing virus but will also eliminate latent virus without perpetual dosing since it has the potential to teach your immune system to do the job on its own (adaptive immunity).Yes- more research has to be done to obtain or prove that goal in humans - maybe a second generation mab has to be developed- but the fact remains it did occur in animal models and was picked by the CHAVI group as the basis of their research for a cure and a vaccine.
That 44million dollars is only a small part of the research dollars going into anti-ps.CHAVI alone has received well over 300million from the Bill and Melinda Gates foundation for their research for a cure and a vaccine and of course the additional dollars poured into the research by other institutions(utsw,Duke,Harvard,pphm etc.). By the way I believe the 44million was the largest grant given by the DOD or the second largest.
Hotpuppy, if you would like to join me in developing this thread for the benefit of all readers, then I will gladly find the links and you can paraphrase for all. But remember that those without a good internet link or a good computer  will still not be able to go to the original docs if your paraphrasing sparks their interest.
Furthermore there is a big difference between something being  the holy grail and asking the question could this be the holy grail.

veritas

Offline veritas

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Re: Could this be the holy grail ?
« Reply #66 on: January 08, 2009, 08:13:41 AM »

Interesting interview by Charlie Rose with Anthony Fauci and David Ho. I wonder what the viral shield from the immune system  is that their talking about?


http://www.charlierose.com/view/interview/9861

Offline bmancanfly

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Re: Could this be the holy grail ?
« Reply #67 on: January 08, 2009, 08:43:41 AM »
thanks for your posts Hotpuppy.
"The trouble with the world is that the stupid are cocksure and the intelligent are full of doubt."

 Bertrand Russell

Offline leit

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Re: Could this be the holy grail ?
« Reply #68 on: January 08, 2009, 07:06:31 PM »

I wonder what the viral shield from the immune system  is that their talking about?
http://www.charlierose.com/view/interview/9861

I think they refer to envelope proteins' sugar coating.
Anyway, what a cheerlessness!  :(


Offline leit

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Re: Could this be the holy grail ?
« Reply #69 on: January 08, 2009, 08:20:29 PM »

Anti-ps [...] will also eliminate latent virus

I'd be not so sure of that: resting HIV infected cells are in a very unique condition and, to the best of my knowledge, it's nowhere stated whether they expose PS or not.

Quote
it has the potential to teach your immune system to do the job on its own (adaptive immunity).

I don't think so: The immune system attacks virions and cells that bavituximab has bound to ONLY BECAUSE it's alerted by bavituximab itself! If a possible adaptive immunity against a SPECIFIC virus (targeted by bavituximab) develops, it's because bavituximab, blunting the infection, gives the immune system TIME to mount SPONTANEOUSLY an effective response before the host is killed. But, since the immune system has proven itself incapable of mounting such a response against HIV, I doubt that bavituximab can make a difference.

That said, if bavituximab will be able to bind to ALL reservoirs' cells, bavituximab + HAART would very probably be the "holy grail": ERADICATION.


Offline veritas

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Re: Could this be the holy grail ?
« Reply #70 on: January 09, 2009, 05:16:18 AM »

leit,

Please read the attached explaining anti-ps in depth with the appropriate references:

http://www.peregrineinc.com/images/stories/media/siteFiles/PSbackgrounder.pdf

PS is located in every cell of the human body. When the cell is infected with some type of pathogen,the cell can no longer hold ps pointing inward (ps flips outward). This flip is a naturally occuring process in the human body when cells are dieing and the immune system leaves them alone. By the way,this flip also occurs in cancer cells. Bavituximab alerts the immune system to this deception and calls the immune system in for the kill.

As far as adaptive immunity is concerned, mice infected with the cmv were treated with Bavituximab and cured. Upon rechallenge by a lethal dose of the virus, the mice were able to fight off the virus on their own with no further dosing of Bavi.
Is Bavituximab THE mab that is going to work? I don't know. the research will tell the story. Perhaps a second generation mab will have to be developed to mount a stronger immune response.

You seem to be interested in the science, so please read the above pdf in depth and let me know what you think. The science is exciting.

veritas

Offline veritas

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Re: Could this be the holy grail ?
« Reply #71 on: January 09, 2009, 08:14:56 AM »

leit,

After reading the above link on anti-ps, here is another link on Bavituximab:


http://www.peregrineinc.com/images/stories/media/siteFiles/20081121_BavituximabAV.pdf

Both these links have been posted before. This second link is a much easier read on Bavituximab but should be read after reading the anti-ps pdf.


veritas

Offline veritas

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Re: Could this be the holy grail ?
« Reply #72 on: January 09, 2009, 08:21:55 AM »

Offline veritas

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Re: Could this be the holy grail ?
« Reply #73 on: January 09, 2009, 08:45:09 AM »



leit,

Then finally read this which is a very important presentation made to NIH then DOD which shows the adaptive immunity component in preclinicals:

http://www3.niaid.nih.gov/Biodefense/PDF/tarvacin.pdf

It was the lassa fever model that showed the adaptive immunity not cmv.

Have I answered your questions?

I'm very exicited about this research and truly believe that this is a breakthrough that we have been waiting for. If the immune response from Bavi is not strong enough to cure, then we will have towait for a second generation mab which I believe they are working on in conjunction with Duke University(please refer to the patents posted at the beginning of this thread). Even if Bavi doesn't cure, we will have I believe a damn good therapy with very few if any side effects since it has shown top line safety data in all humans tested to date(more than 100 for both virus and cancer).

This research is definitely a watcher!

veritas

Offline veritas

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Re: Could this be the holy grail ?
« Reply #74 on: January 09, 2009, 12:32:32 PM »
More evidence of anti-ps as a safe therapeutic for various viral diseases:


http://microbiologybytes.wordpress.com/

"cellular toxicity by the virus led to the exposure of ps".

Direct clearance of infectious virus from the blood and antibody-dependent cellular cytotoxicity of virus-infected cells seemed to be the major antiviral mechanisms.
« Last Edit: January 09, 2009, 12:35:34 PM by veritas »

Offline veritas

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Re: Could this be the holy grail ?
« Reply #75 on: January 09, 2009, 12:59:19 PM »
I think they refer to envelope proteins' sugar coating.
Anyway, what a cheerlessness!  :(


leit,
I agree the interview was cheerlessness but I was being somewhat facetious when asking what the shield was. Flipped PS shields the virus from the immune system. I believe both researches are being very cautious about what they say,thus the cheerlessness.

veritas

Offline bimazek

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Re: Could this be the holy grail ?
« Reply #76 on: January 10, 2009, 05:15:48 AM »
i havent read all of this but it looks very good
extremely exciting stuff

35 years ago or however long ago the first idea of a Mab monoclonal anti body was thought of, at that time they were suppose to be the holy grail of many diseases it just took alot longer to develop all of them for many diseases than science thought

i just posted a list of Mab that treat diseases in living with hiv section

supposedly theoretically they should have zero or low side effects or at least many orders of magnitutude less than chemical meds,

do you all understand difference between a chemical med and a Mab, monoclonal antibody

anyway

very very good news

i think this would be considered the best news i have seen in years

why because it is a Mab

and i remember 20 or 30 years ago or more Mab's were suppose to be the thing that would treat disease safely effectively without poisoning the human body

these are

fully human monoclonal antibodies folks, that means that they are as perfect as homo sapien, i mean yes there may be a few who have very unusual genetic make up who would have a reaction but since they are build in the form of human antibodies this should be very low

first thing is read the definition of all these terms in wiki to  get idea

nti-PS and monoclonal AB are two paths that researchers are evaluating.

keep posting

like where are the trials!!!!!!

i think we should all do some kind of protest when it gets thru 3rd phase demanding

wide spread use of this in usa

esp. since so many have so so so so many terrible side effects from the meds

i totally support HAART and no one should stop taking it unless discussed with thier doctor
and in my opinion everyone should start as soon as they find out poz if they have any problems, mental confusing can be sign of hiv in body, as well as any of the t cells under 500 should start asap

anyway

thanks

Offline bimazek

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Re: Could this be the holy grail ?
« Reply #77 on: January 10, 2009, 05:25:12 AM »
http://www.peregrineinc.com/index.php?option=com_content&task=view&id=30&Itemid=46
animaitons  and video


is this amazing link with animation anywhere on this post??

my eyes are getting weaker and seeing text is harder than in past

this has amazing stuff

http://www.peregrineinc.com/index.php?option=com_content&task=view&id=20&Itemid=36

Offline bimazek

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Re: Could this be the holy grail ?
« Reply #78 on: January 10, 2009, 06:00:28 AM »
could  DNA-altered animals produce fully human monoclonal antibodies?  I think they can right???

New old-fashioned drug makers: goats
Los Angeles Times - 2 hours ago
A herd has been genetically engineered to make a human protein in their milk that can prevent dangerous blood clots. If the drug is approved by the FDA, the barn door could swing open.
US advisers back 1st drug from DNA-altered animals Reuters

http://www.latimes.com/news/nationworld/nation/la-sci-geneticmilk10-2009jan10,0,242781.story

http://uk.reuters.com/article/scienceNewsMolt/idUKTRE50873T20090110

Offline veritas

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Re: Could this be the holy grail ?
« Reply #79 on: January 10, 2009, 06:04:47 AM »

Bim,

Thanks for your kind words.

Those video links are amazing and I thank you for posting them.

They are doing the combination HepC/Hiv trial but I believe they are leaving the strictly HIV trials to CHAVI. I also believe that CHAVI is going for the "Homerun" so its a matter of waiting for CHAVI to release information. Since CHAVI is under a microscope (media wise), they seem to do testing 9 ways to Sunday before releasing any information. That's a good thing I guess but the wait is frustrating.

Your absolutely right when it comes to mabs vs chemicals, however, mabs can somtimes have adverse effects (WHEN YOUR IMMUNE SYSTEM ATTACKS YOUR OWN BODY).Usually,I believe, areaction like that happens fairly quickly but all mabs should be developed with caution. Bavituximab has shown no adverse reactions and as a matter of fact has shown top line safety data in trials thus far in humans.
I will definitely be following this research closely and please if you find any more info don't hesitate to post, your contributions are welcome and appreciated.

veritas

Offline veritas

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Re: Could this be the holy grail ?
« Reply #80 on: January 10, 2009, 09:14:05 AM »

Offline leit

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Re: Could this be the holy grail ?
« Reply #81 on: January 10, 2009, 08:36:03 PM »

Have I answered your questions?

Dear "veritas",

I had already read what you mentioned (and more), but...

I'm NOT interested in bavituximab IN ITSELF, nor in bavituximab & cancer, nor in bavituximab & CMV, nor in bavituximab & HCV... nor even in bavituximab & HIV, but ONLY in bavituximab & HIV RESERVOIRS.
Moreover, I think that trying to infer something from "bavituximab & X" is only wasted time, if "X" is not "HIV RESERVOIRS".

That said, I can only repeat that it's nowhere stated whether HIV latent reservoirs' cells expose PS or not and, consequently, whether bavituximab could be effective against them or not.
Since this is THE problem (HIV infection is still incurable only because of reservoirs, otherwise HAART would be enough), Peregrine Pharmaceuticals' silence on the matter arouses my suspicions.


Current trials confirm that. Please look at http://clinicaltrials.gov/ct2/show/NCT00503347:

Bavituximab Repeat-Dose Trial in Patients Co-Infected With Chronic Hepatitis C Virus and Human Immunodeficiency Virus

Secondary Outcome Measures:
- Blood levels of [...] HIV RNA

Inclusion Criteria:
- Chronic hepatitis C infection based on history and detectable serum HCV RNA

Exclusion Criteria:
- [...] HIV antiviral therapy within 4 weeks of Day 0


If they would have meant to prove effectiveness of bavituximab on reservoirs, what above should have read:

Bavituximab Repeat-Dose Trial in Patients Infected With Human Immunodeficiency Virus

Secondary Outcome Measures:
- Blood levels of HIV DNA

Exclusion Criteria:
- Chronic hepatitis C infection based on history and detectable serum HCV RNA

Inclusion Criteria:
- Viral load < 50 copies/ml for at least the previous 12 months (*)
- Taking HAART (*)

(*) From: Valproic Acid and Its Effects on HIV Latent Reservoirs


Bottom line: Peregrine Pharmaceuticals' folks seem to be the first who don't believe in bavituximab potential against reservoirs.
« Last Edit: January 10, 2009, 09:43:13 PM by leit »

Offline J220

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Re: Could this be the holy grail ?
« Reply #82 on: January 10, 2009, 10:23:45 PM »

Bottom line: Peregrine Pharmaceuticals' folks seem to be the first who don't believe in bavituximab potential against reservoirs.

Why would they have it listed as a secondary outcome if they did not believe it may have potential? If it was not part of the clinical protocol and target for the trial they would not even mention 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 leit

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Re: Could this be the holy grail ?
« Reply #83 on: January 10, 2009, 10:42:53 PM »
"It" WHAT, please, "J220"???

« Last Edit: January 10, 2009, 10:45:41 PM by leit »

Offline J220

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Re: Could this be the holy grail ?
« Reply #84 on: January 10, 2009, 10:48:41 PM »
The effect on reservoirs....//////////
« Last Edit: January 11, 2009, 01:18:21 AM 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 leit

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Re: Could this be the holy grail ?
« Reply #85 on: January 10, 2009, 11:00:46 PM »

The effect on reservoirs is measured through HIV-DNA, not HIV-RNA.
« Last Edit: January 11, 2009, 02:08:22 AM by leit »

Offline J220

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Re: Could this be the holy grail ?
« Reply #86 on: January 10, 2009, 11:08:28 PM »
Uhh, yeah, but if you are on HAART, you nevertheless have low-level replication. If after starting this therapy the levels of RNA are reduced or dissapear, what do you think the reason for this could be? In addition, the company specifically talks about the potential of this therapy in regards to HIV-infected cells and enveloped viruses. Listen, no one is telling you to believe this can work, but it's a large leap to say that Peregrine doesn't believe in the potential address reservoirs. What else do you think they are talking about?
« Last Edit: January 11, 2009, 01:19:02 AM by J220 »
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Offline veritas

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Re: Could this be the holy grail ?
« Reply #87 on: January 11, 2009, 07:35:03 AM »

leit,

latent cell reservoirs are resting cd4 cellls infected with the virus non-replicating.Any cell in the body that is infected with the virus flips Ps. (see the video posted by Bimazek). PS does not flip back when the cell is resting. Also, the exposed ps is protecting the infected cell from the immune system.
J220 gets it.
The problem is going to come in the form of mounting a strong enough antibody response to eradicate the virus. However, if the mab is able to teach the immune system how to go after flipped ps on its own, like it did in the mouse models,our discussion could be a mute point. The research will tell.

veritas


Offline veritas

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Re: Could this be the holy grail ?
« Reply #88 on: January 11, 2009, 07:50:55 AM »
Please read this again:


Nature Reviews Drug Discovery 8, 19 (January 2009) | doi:10.1038/nrd2788

http://www.nature.com/nrd/journal/v8/n1/full/nrd2788.html

Antiviral Drugs: Exposed target for broad-spectrum antivirals
Man Tsuey Tse

Phosphatidylserine, the most abundant anionic phospholipid of the plasma membrane, has been used as a target to develop a novel broad-spectrum antiviral agent called bavituximab. Strikingly, bavituximab was able to cure overt disease in guinea-pigs infected with a potentially lethal dose of Pichinde virus, a model of Lassa fever virus.

Writing in Nature Medicine, Thorpe and colleagues proposed that the effects of a wide range of viruses on host cells could lead to normally intracellular anionic phospholipids being exposed on the surface of infected cells. To test this hypothesis, they used bavituximab a chimeric antibody that binds to complexes of the phosphatidylserine-binding plasma protein 2-glycoprotein 1 and anionic phospholipids. These experiments showed that infection of mouse cells by Pichinde virus led to phosphatidylserine exposure, and that bavituximab binds to virus-infected cells and infectious virions.

Treatment of guinea-pigs infected with a normally lethal dose of Pichinde virus with bavituximab 67 days after infection led to 50% of the animals surviving, and clearance of the virus was observed by day 135. In addition, combination of bavituximab with ribavirin (the current drug of choice for treating Lassa fever) had an additive effect.

The authors also provided evidence for two mechanisms that seem to underlie these effects. First, bavituximab treatment clears infectious virus from the bloodstream. Second, it induces antibody-dependent cellular cytotoxicity of virus-infected cells. As the authors propose, it seems that phosphatidylserine on virions and infected cells might enable viruses to evade immune recognition and dampen inflammatory responses, and that bavituximab interferes with this 'masking' process.

Finally, the authors explored phosphatidylserine exposure in other viral infections. Exposure was also observed in cells infected with influenza virus, vaccinia, vesicular stomatitis virus and mouse cytomegalovirus (CMV). This indicates that this process is a common feature of enveloped viruses; exposure could also extend to non-enveloped viruses. Furthermore, tests in mice infected with an almost lethal dose of CMV showed that all treated mice survived, in contrast to untreated mice, of which only 25% were alive after 96 days.

In both animal models, bavituximab was well tolerated, and no toxicity was observed histologically. Therefore, targeting phosphatidylserine shows promise as an antiviral strategy. In addition, as phosphatidylserine is a host-derived target, the development of resistance could be limited. Clinical trials of bavituximab are currently underway in patients with hepatitis C co-infected with HIV.

References and links
ORIGINAL RESEARCH PAPER
Soares, M. M., King, S. W. & Thorpe, P. E. Targeting inside-out phosphatidylserine as a therapeutic strategy for viral diseases. Nature Med. 23 Nov 2008 (doi: 10.1038/nm.1885)

Offline leit

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Re: Could this be the holy grail ?
« Reply #89 on: January 11, 2009, 06:53:05 PM »

if you are on HAART, you nevertheless have low-level replication. If after starting this therapy the levels of RNA are reduced or dissapear, what do you think the reason for this could be?

We are not playing hide-and-seek! The reservoirs' marker is HIV-DNA, not HIV-RNA. Period.

Quote
In addition, the company specifically talks about the potential of this therapy in regards to HIV-infected cells

HIV-infected cells are not necessarily resting latently infected cells (i.e. reservoirs). In fact, they behave very differently.

Quote
it's a large leap to say that Peregrine doesn't believe in the potential address reservoirs. What else do you think they are talking about?

About one of the many drugs which do nothing against reservoirs.
« Last Edit: January 11, 2009, 07:13:36 PM by leit »

Offline leit

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Re: Could this be the holy grail ?
« Reply #90 on: January 11, 2009, 07:07:58 PM »

latent cell reservoirs are resting cd4 cellls infected with the virus non-replicating.Any cell in the body that is infected with the virus flips Ps.

WHEN does it flip it? When HIV fuses with the receptors, when it actually enters the cell, when it reverse-transcripts its RNA into DNA, when this DNA integrates into the cell genome... when new virions bud out? WHEN EXACTLY?
If this "when" is "at the very beginning", then bavituximab could be fully effective against reservoirs, otherwise not (a T cell can become resting in any moment).

Quote
The problem is going to come in the form of mounting a strong enough antibody response to eradicate the virus.

The problem is whether ALL (if ANY!!!) reservoirs' cells expose PS, so that bavituximab can bind to them.

Quote
if the mab is able to teach the immune system how to go after flipped ps on its own, like it did in the mouse models

I've already told you that bavituximab teaches NOTHING. The mice developed SPECIFIC immune responses against SPECIFIC viruses only because bavituximab, blunting the infection, gave them time to SPONTANEOUSLY do that before they were killed by those viruses.
The only thing bavituximab can teach the immune system is to develop anti-chimeric antibodies that render bavituximab itself completely ineffective; definitely not a good lesson!
« Last Edit: January 11, 2009, 08:02:40 PM by leit »

Offline veritas

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Re: Could this be the holy grail ?
« Reply #91 on: January 12, 2009, 05:39:35 AM »
WHEN does it flip it?

The problem is whether ALL (if ANY!!!) reservoirs' cells expose PS, so that bavituximab can bind to them.

I've already told you that bavituximab teaches NOTHING. The mice developed SPECIFIC immune responses against SPECIFIC viruses only because bavituximab, blunting the infection, gave them time to SPONTANEOUSLY do that before they were killed by those viruses.
The only thing bavituximab can teach the immune system is to develop anti-chimeric antibodies that render bavituximab itself completely ineffective; definitely not a good lesson!

PS flips as soon as the virus enters the cell due to cellular stress. (see video)

Bavi should be effective against the reservoirs if the immune response is strong enough.

The infection is not blunted but destroyed by the immune system by Bavi.s call to arms. (see video)

Please provide reference where Bavi is ineffective due to the development of anti-chimeric antibodies. If that were the case then redosing Bavi would be a problem as they are doing in clinical trials. It would have been interesting to see if that mouse cured with lassa fever had been rechallenged with a different retrovirus to see if the immune system was able to fight it off. Maybe they are doing it. But if Bavi or some next generation Bavi is being developed for bio-terrorism, then I guess the immune system can be TAUGHT to recognize exposed ps.


Offline veritas

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Re: Could this be the holy grail ?
« Reply #92 on: January 12, 2009, 09:31:52 AM »

Aids Vaccine Conference 2008: summary from NIAD



http://www3.niaid.nih.gov/topics/HIVAIDS/Research/vaccines/reports/aidsvac2008.htm


Broadly neutralizing antibodies take center stage and a better BAVI is talked about (antibody- 2G12).


Offline veritas

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Re: Could this be the holy grail ?
« Reply #93 on: January 13, 2009, 05:00:16 PM »
Vaccine research pre-clinical - the vaccine worked in monkeys using mabs:

I forgot to add the reference (was too excited)

Long-term vaccine protection from AIDS and clearance of viral DNA following SHIV89.6P challenge


http://www.ncbi.nlm.nih.gov/pubmed/19135115?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

Schell J, Rose NF, Fazo N, Marx PA, Hunter M, Ramsburg E, Montefiori D, Earl P, Moss B, Rose JK.
Yale University School of Medicine, New Haven, CT, United States.

In an earlier study, our group vaccinated rhesus macaques with vesicular stomatitis virus (VSV) vectors expressing Gag, Pol, and Env proteins from a hybrid simian/human immunodeficiency virus (SHIV). This was followed by a single boost with modified vaccinia virus Ankara (MVA) vectors expressing the same proteins. Following challenge with SHIV89.6P, vaccinated animals cleared challenge virus RNA from the blood by day 150 and maintained normal CD4 T cell counts for 8 months. Here we report on the long-term (>5-year post-challenge) status of these animals and the immunological correlates of long-term protection. Using real-time PCR, we found that viral DNA in peripheral blood mononuclear cells (PBMCs) of the vaccinees declined continuously and fell to below detection (<5copies/10(5)cells) by approximately 3 years post-challenge. SHIV DNA was also below the limit of detection in the lymph nodes of two of the four animals at 5 years post-challenge. We detected long-term persistence of multi-functional Gag-specific CD8(+) T cells in both PBMCs and lymph nodes of the two protected animals with the Mamu A*01(+) MHC I allele. All animals also maintained SHIV89.6P neutralizing antibody titers for 5 years. Our results show that this vaccine approach generates solid, long-term control of SHIV infection, and suggest that it is mediated by both cytotoxic T lymphocytes and neutralizing antibody.
« Last Edit: January 13, 2009, 05:33:01 PM by veritas »

Offline leit

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Re: Could this be the holy grail ?
« Reply #94 on: January 14, 2009, 12:10:26 AM »

PS flips as soon as the virus enters the cell due to cellular stress. (see video)

Sorry, but I trust no longer in "WMF-drugs", nor in "Flash-drugs", nor in (fraudulent!) "Real-drugs". Peer-reviewed publications, please!

Quote
Please provide reference where Bavi is ineffective due to the development of anti-chimeric antibodies.

At the moment I cannot, nor I said this will happen. But, unfortunately, that's not an uncommon immune reaction against chimeric antibodies like bavituximab.

Quote
if Bavi or some next generation Bavi is being developed for bio-terrorism, then I guess the immune system can be TAUGHT to recognize exposed ps.

NO! Bavituximab teaches NOTHING! It is NOT an antigen which arouses a WHOLE and PERMANENT anti-viral immune response againt PS-exposing viruses, but only an antibody which, WHEN injected, annihilates viruses and infected cells CURRENTLY exposing phosphatidylserine.


Offline veritas

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Re: Could this be the holy grail ?
« Reply #95 on: January 14, 2009, 09:50:24 AM »

leit,

Did you read this post above?

HIV - Phosphatidylserine Breakthrough

That post has all thepeer review
you need if one bothers to read the references.


"At the moment I cannot, nor I said this will happen. But, unfortunately, that's not an uncommon immune reaction against chimeric antibodies like bavituximab."

You will not find any with Barvituimab!


"NO! Bavituximab teaches NOTHING! It is NOT an antigen which arouses a WHOLE and PERMANENT anti-viral immune response againt PS-exposing viruses, but only an antibody which, WHEN injected, annihilates viruses and infected cells CURRENTLY exposing phosphatidylserine."

Bavituximab does NOT annihilate viruses and infected cells exposing PS! Barvi alerts the immune system to annihilate viruses and infected cells exposing ps. Please do somemore research on the moa of Bavi.



Offline leit

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Re: Could this be the holy grail ?
« Reply #96 on: January 14, 2009, 05:57:41 PM »

Ok, "veritas", now I'm fed up.

Good luck to you and to your messed-up personal, imaginary bavituximab!


Offline veritas

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Re: Could this be the holy grail ?
« Reply #97 on: January 15, 2009, 03:47:46 AM »

  Never go to war unarmed!

Offline georgep77

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Re: Could this be the holy grail ?
« Reply #98 on: January 15, 2009, 08:25:36 AM »
Lol

              :D

           The time will tell, the winner of this battle
Come on Sangamo,  Geovax,  Bionor immuno, ...Make us happy !!!
+ 2008

Offline David Evans

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Re: Could this be the holy grail ?
« Reply #99 on: January 15, 2009, 10:53:23 AM »
I'm not sure what the point of this whole "battle" is other than egos. Veritas and Leit are both arguing with a level of certainty that kind of astonishes me. It reminds me of the drunken/stoned philisophical arguments that seemed kind of interesting in Freshman year of college, but look silly now in hindsight.

The research on PS and bavituximab is in it's infancy. The sign of any researcher worth his or her salt is not the religious fervor and certainty with which they argue for a pet theory, but the ability to make a reasoned statement, after addressing the caveats. I hear no caveats.

Veritas is correct, as far as the research can tell us so far, that the PS does appear to flip with some infectious agents (not all), for reasons that are not yet clearly spelled out. What the scientists are proposing still needs to be more completely validated. There's some good data, but some it is also theory at this point. Bavituximab also appears, so far, to assist the immune system in recognizing these infected cells that would otherwise escape notice. It seems likely that this would apply to latently infected cells as well, but that's still theoretical until the clinical trials are conducted. That's about as far as anyone can go, based on the research that's been conducted so far.

The molecular interplay between the immune system and HIV is far too complex to do more than theorize any of the rest of it at this point. We've all seen even more promising and well documented HIV research amount to nothing, because of unanticipated complications. I'd encourage you guys to cool your jets on this until more clinical and basic research becomes available.

-David

 


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