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Author Topic: New 'OPAL Therapy' simple, cost-effective method of treating HIV infection  (Read 5578 times)

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Offline datdude

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New 'OPAL Therapy' presents simple, cost-effective method of treating HIV infection
Australian researchers have unveiled a new immunotherapy technique to help prevent the progression from HIV infection to AIDS. Details of the simple, cost-effective technique are published May 2nd in the open-access journal PLoS Pathogens.

There is an overwhelming need for effective immunotherapies for HIV, as current therapies are expensive, impractical, and often highly toxic. The authors, led by Professor Stephen Kent, propose a technique named OPAL therapy—Overlapping Peptide-pulsed Autologous CeLls—a reinfusion of fresh blood cells incubating with overlapping SIV peptides. The OPAL technique was successfully tested in animal trials for stimulation of immunity, control of virus levels, and prevention of AIDS.

Vaccination diminished the levels of virus 10-fold lower than in controls, and was shown to be durable for over one year past initial vaccination. Therefore, viral replication was shown to be prolonged and more manageable, resulting in fewer deaths from AIDS.


###
The study is the result of collaboration among researchers from the University of Melbourne, the National Serology Reference Laboratory, and the University of New South Wales. The researchers plan to conduct future OPAL-therapy clinical trials in HIV-infected humans.


Offline bimazek

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this looks interesting
i believe there was some other posts but this may be a result of more trials and more successful or larger treatment group
i bet that aussie land would give just about anything to jump ahead of old USA in this for prestige and not least of which is the money rewards
i would not be surprised if this good news
perhaps a link to the older trials that were posted is helpful

the thing i always liked about the aussies is they cut thru the b.s.
they get things done and they do not worship authority and they are not politically correct
so refreshing

i spent 4 months there , two summers, in the early 90s

amazing people beaches everything


Offline Ann

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Datdude,

Would you please link to the original article when you lift things off the internet? Please read the Research forum's Welcome Thread , where you'll find the posting guidelines, before posting in this forum again. Thanks!

I believe the article you posted comes from here and you missed out an important part:

PLEASE ADD THIS LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT: http://www.plospathogens.org/doi/ppat.1000055

Ann
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"...health will finally be seen not as a blessing to be wished for, but as a human right to be fought for." Kofi Annan

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Offline John2038

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On the same subject, this other link: http://uninews.unimelb.edu.au/articleid_2109.html

Australian researchers have made a major discovery in the fight against AIDS, with the development of a novel, simple and safe technique for boosting the body’s immune response to deadly viruses like HIV, which is even effective against drug resistant forms of the disease.

Associate Professor Stephen Kent from the University of Melbourne’s Department of Microbiology and Immunology says the findings hold great promise for the treatment of HIV, other chronic viral infections, and drug resistant infections, which are becoming a major problem.

“We have invented a simple new technology to boost the ability of the immune system to fight chronic infections such as AIDS and Hepatitis C. This involves using a patient’s own blood treated with small overlapping proteins of the virus (called peptides),” Associate Professor Kent says.

The research will be published today in the Journal of Virology.
**Images of Associate Professor Kent and his research team are available.

The researchers call the therapy Overlapping Peptide Pulsed Autologous Cells (OPAL). They have been awarded National Health and Medical Research Council (NHMRC) funding of almost $500,000 to refine the technique so that it can be studied in humans.

“The ability to induce and expand the immune response across most or all parts of the virus is highly advantageous. Our results, which consistently demonstrated sharply enhanced immunity in vaccinated animals, suggest that this therapy could also work in humans.”

The researchers initially set out to develop a technique for measuring the effectiveness of a HIV vaccine. They first extracted blood from previously vaccinated animals and then coated the cells with HIV peptide markers (a technique which only takes an hour to complete).

In a normal situation, when HIV or any virus infects a cell, it leaves behind tell-tale markers or peptides on the cell surfaces which tell the immune system that the cell is infected. In this study, the researchers did not infect the animals with HIV, but rather created the illusion to the body that these cells were infected because they had the tell-tale markers (peptides) on their surface.

When they injected this peptide-coated blood back into the vaccinated animals they found that it triggered a huge immune response.

“When we analysed HIV-specific immunity in the weeks following the assays (peptide-coating), a marked enhancement of virus-specific immunity was induced,” Associate Professor Kent says.

“The technique was also effective for boosting the immune response to Hepatitis C peptides and we believe that it could be refined for many different viral infections and cancers. We have also shown it can be used to induce immune responses against drug resistant forms of HIV. The OPAL technique is simpler than current cell-based vaccine techniques which usually require isolation of rare specialised cells from blood.”

Associate Professor Kent led a dedicated team of scientists, Ms Socheata Chea, Dr Jane Dale and Dr Rob De Rose at the University of Melbourne’s Department of Microbiology and Immunology, and collaborated with colleague Dr Ian Ramshaw at the Australian National University’s John Curtin School of Medical Research.

Associate Professor Kent says there is an urgent need to develop simple methods to induce or enhance HIV-specific immunity to prevent or control the disease. “Our research is a major step forward in this regard.”

The researchers will now embark on a series of experiments to refine the technique to make it even more practical and generate even bigger responses. Associate Professor Kent’s group plans to begin human testing of the OPAL therapy in the next one to two years.


More information about this article:

Elaine Mulcahy
Media Liaison
emulcahy@unimelb.edu.au
8344 9806


Stephen Kent
Microbiology and Immunology
8344 9939
0438 290 994
skent@unimelb.edu.au

Offline bimazek

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anyone in Aussie land who can get in on the human trial and post here...

 http://www.plospathogens.org/article/fetchArticle.action?articleURI=info:doi/10.1371/journal.ppat.1000055

excerpts from 27 page long science document....

A simple intermittent immunotherapy that reduces the need for long-term antiretroviral therapy (ART)

We recently reported the robust T-cell immunogenicity of treating unfractionated whole blood or peripheral blood mononuclear cells (PBMC) with overlapping peptides of SIV, HIV-1 virus in outbred pigtail monkeys [8],[9]. We termed this simple immunotherapy OPAL (Overlapping Peptide-pulsed Autologous ceLls). This technique is attractive since there is no prolonged ex vivo culture of antigen-presenting cells, robust CD4 and CD8 T-cell responses to both structural and regulatory proteins can be induced, and peptide antigens are simple to manufacture to high purity.

In summary, OPAL immunotherapy, either using overlapping Gag SIV peptides or peptides spanning the whole SIV proteome was highly immunogenic and resulted in significantly lower viral loads and a survival benefit

This study added peptides to PBMC, however we have shown an even simpler technique, adding peptides to whole blood is also highly immunogenic, a technique that will be more widely applicable

This is one of the largest therapeutic SIV vaccine studies yet reported

In the end, the vaccination process was both safe and effective.

How well the findings on OPAL immunotherapy translate to humans with acute HIV-1 infection will be determined by clinical trials. Virus-specific CD4 T cells are typically very weak in HIV-infected humans or SIV-infected macaques; dramatic enhancement of these cells were induced by OPAL immunotherapy and this may underlie its efficacy.

OPAL immunotherapy with Gag peptides is proceeding into initial trials in HIV-infected humans. Additional peptides can readily be added into standard consensus strains mixes to cover common strain or subtype variations between strains with this technology [!!!!!!!!!!!!!!!!!! -- this is good news works for all strains]

"The pattern of enhancement of T cell immunity was similar for the first and second vaccination sets.  [--- this means that if they give the vaccine many weeks after the first vaccine it is dramatically just as effective as the first time! ]

To further assess the durability of SIV control and prevention of disease with OPAL immunotherapy, we re-boosted all 32 animals in the same randomized groups 3 times with the identical procedure (at week 36, 39, 42) without ART cover and followed the animals for an additional 6 months. Despite the lack of ART cover, SIV-specific T cell immunity was dramatically enhanced in immunized animals 2 weeks after the last vaccination, similarly to the primary vaccination (Figs 1, 2). . The pattern of enhancement of T cell immunity was similar for the first and second vaccination sets.
« Last Edit: May 03, 2008, 01:51:44 PM by bimazek »

Offline bimazek

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http://www.google.com/search?hl=en&q=OPAL+Therapeutics&btnG=Google+Search
from the paper above
Competing interests: SJK spun out a venture capital–backed biotechnology start-up company, OPAL Therapeutics Pty Ltd, to pursue this technology towards clinical trials. SJK, CJB and the University of Melbourne hold shares in this company. AJH has been an employee of OPAL Therapeutics.
http://72.14.253.104/search?q=cache:zxKcEHte9kYJ:www.aids2006.org/Web/THAA0101.ppt+OPAL+Therapeutics&hl=en&ct=clnk&cd=12&gl=us

http://www.gbsventures.com.au/portfolio.htm

http://www.altapartners.com/portfolio_sector.php?id=1

http://sec.edgar-online.com/2006/04/28/0000950134-06-008267/Section4.asp
The following is an excerpt from a DEF 14A SEC Filing, filed by DYNAVAX TECHNOLOGIES CORP

is this OPAL the same thing as the
DYNAVAX TECHNOLOGIES CORP ???

Offline bimazek

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http://www.plospathogens.org/article/fetchArticle.action?articleURI=info:doi/10.1371/journal.ppat.1000055

excerpted .... so anyone can understand...  basically they took the blood out of a SIV infected monkey, they added saline and then some SIV peptides, they got some from NIH, then they used DMSO to mix it all nastily together, then they gently shook, shake and gave the blood a water bath, at cozy room temperature for one hour.  By then they hoped that the immune cells in the blood were super turned on to attack SIV which they were... then they injected the whole mess of blood back in the monkeys...   basically sounds like we could all do this in the kitchen if we were in a pinch....  they say it is inexpensive  and not complicated and very inexpensive ...

animals were immunized with OPAL immunotherapy using thier own SIV infected peripheral blood mononuclear cells (PBMC) were isolated  from 18 ml of blood (anticoagulated using Heparain).

All isolated PBMC (on average 24 million cells) were suspended in normal saline to which either a pool of SIVmac  Gag peptides or 823 peptides spanning all SIVmac proteins (Gag, Pol, Env, Nef, Vif, Tat, Rev, Vpr, Vpx) were added at 10 µg/ml of each peptide within the pool.

Peptides were overlapping by 11 amino acids 80% purity kindly provided by the NIH AIDS reagent repository program (catalog numbers 6204, 6443, 6883, 6448-50, 6407, 8762, 6205).

To pool the peptides, each 1 mg vial of  peptide was solubilized in pure DMSO and added together.

The concentration of the SIV Gag and All peptide pools was pulsed onto cells at 10 µg/ml regardless of vaccine type.

The peptide-pulsed PBMC blood were held for 1 hr in a 37°C waterbath, gently vortexed every 15 minutes and then, without washing, reinfused IV into the same animal.

[judging from these complex diagrams it looks to me like we would, if this works the same in humans as monkeys need to get this whole blood peptide treatment once every 6 months based on the numbers]

http://www.plospathogens.org/article/slideshow.action?uri=info:doi/10.1371/journal.ppat.1000055&imageURI=info:doi/10.1371/journal.ppat.1000055.g002


[this graph does look very encouraging and  to me it looks like this OPAL procedure basically cuts viral load in half for many many months, but the question is how to cut it in half over and over so viral load is undetectable?? perhaps treatments every 2 months, what looks really exciting is that with OPAL treatment none died (zero) or 90% of the  animals were alive (depending if they got OPAL gag or OPAL all peptides) 

 but with out OPAL 50% died by the end of 64 weeks (remember that the monkeys have a shorter life span so this is about the same as 10 to 15 years in humans) in other words, with OPAL no monkeys died at all without it 50% died of aids or monkey aids, remember that the monkey model they have now,
using a special SIV is very close to human disease progression it is a good model.

http://www.plospathogens.org/article/slideshow.action?uri=info:doi/10.1371/journal.ppat.1000055&imageURI=info:doi/10.1371/journal.ppat.1000055.g002#

SIV peptides are defined as little pieces of virus proteins

these peptides about 10 of them stimulate the immune cells in the blood that is taken out of the monkeys what seems to work is that the peptides/proteins are mixed together for over an hour with the immune cells of the blood about 15ml (not very much blood really) and this give the immune cells a much stronger chance to recognize the pieces of the virus particles than the immune cells would inside the body,

 inside the body the virus particles are hidden behind a fat covering and many other factors, what is different about this technique than a regular vaccine this is kind of a super giant vaccine made with your own blood and with the peptides of the virus and then the blood with immune cells and the peptides of the virus are mixed around for an hour to get them very well acquainted and by that time the immune cells of the blood have decoded and figured out the shape and the size and the fact that this is a big big nasty thing and so they are primed to attack,   

 a flu vaccine is very similar but the mixing and such is done inside the body after the injection

if you saw the movie John Adams and you saw the time when Laura Lynnie and her family got the pox vaccination, that type of -- in the old days -- style vaccination is very close to what this technique is... in the   movie John Adams and you saw the time when Laura Lynnie and the family got vaccinated, the doctor had a poor suffering boy on the back of the cart covered with millions of pox oozing sores and the doctor went out to the cart and took a needle or really a knife pretty big and poked it around in the pus sore of this poor boy who had pox literally getting a big hunk of cells and blood and ooze from the pox sore  -- basically a glob of cells pox and blood...

then the doctor went into the house and cut the arm of each family member and then in a 45 second INOCULATION tore the bleeding skin of the person and mixed the glob in the fluid and actual cells and all kinds of parts of  the pox cells  virus into the wound

and then the person got a mild case of the pox, in some cases, but this was better than getting the pox air born in the lungs

so this technique from aussie land    is kind of similar to this mixing of the biologically active components of the virus peptides with the persons blood and body, in 1776 it was done by cutting the arm and then mixing in the fluids and cells from a living victim of the disease who was on the back of a cart, now only it is done in a more scientific way  with the mixing down in a dish and then re-infused into the human body.

i always thought that there must be a way to vaccinate this way for hiv

BTW when Salk the inventor of the polio vaccine was asked in 1983 how to create a hiv vaccine he said simple, just take the virus you have now isolated and expose it to formaldehyde and then inject it, they tried that and it didn't work, imagine if the 1776 method would have worked.  BTW was there not a group of africans who got exposed dozens and hundreds of times and they seems to have a immune response that kept VL very very low? kind of similar to this OPAL inoculation.

Ex vivo inoculation because the mixing is done outside the body is the OPAL technique

 


« Last Edit: May 04, 2008, 09:59:28 PM by bimazek »

Offline bimazek

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i am only human and prone to hope and excitement but the more i think about this chart, graph, i am not sure
how or if this is a breakthrough or not, the issue is Yes 50% reduction in VL but i need 99% reduction or i am not buying it, perhaps if they do it over and over, i do not know, it is early and there is a ton more good that come out of this and yes this could be and would be a huge breakthrough if it can be perfected in humans

http://www.plospathogens.org/article/slideshow.action?uri=info:doi/10.1371/journal.ppat.1000055&imageURI=info:doi/10.1371/journal.ppat.1000055.g002#

Offline hahaha

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i am only human and prone to hope and excitement but the more i think about this chart, graph, i am not sure
how or if this is a breakthrough or not, the issue is Yes 50% reduction in VL but i need 99% reduction or i am not buying it, perhaps if they do it over and over, i do not know, it is early and there is a ton more good that come out of this and yes this could be and would be a huge breakthrough if it can be perfected in humans

http://www.plospathogens.org/article/slideshow.action?uri=info:doi/10.1371/journal.ppat.1000055&imageURI=info:doi/10.1371/journal.ppat.1000055.g002#

I gotta say it is good enough for me.  I WANT TO STOP HAART!!! Even a three months vacation will make me feel happy like heaven!! I don't mind vaccinate again and again, or take HAART on and off, as long as I can have a BREAK for that. 

I hope I hope I hope, this OPAL thing can be verified ASAP, so at least, I have a chance to stop HAART on or before 2010.   
Aug 9, 2006 Get infected in Japan #$%^*
Oct 2006 CD4 239
Nov 2006 CD4 299 VL 60,000
Dec 1, Sustiva, Ziagan and 3TC
Jan 07, CD4 400

Offline bimazek

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I made a mistake in reading a graph.  The graph was log. -  logarithmic.  So what I saw as a 50% reduction in VL is actually a 90% reduction in VL!!!  This is great news.  This means that the results are very very exciting and powerful.   In the post above where i say

 50% reduction in VL
in should say
 90% reduction in VL

which is even better and I could live with.  Can someone contact this University in Aussie land and find out when and where the trials are going to start!

Many great great days in hiv research and science.  We are all so so lucky today with this many many different advances and many new kinds of HAART and many new meds coming out in the pipeline.


Offline bimazek

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is there anyone in Australia that can find out when these human trials will start?

Offline parteboy

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Steven Kent is actually my HIV specialist and I'll ask him at my next appointment.

Offline hahaha

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Steven Kent is actually my HIV specialist and I'll ask him at my next appointment.

Anybody knows any update for that?  This is the most practical and realistic thing in the foresee-able future. Especially after KP-1461 slow down the progress.....

 
Aug 9, 2006 Get infected in Japan #$%^*
Oct 2006 CD4 239
Nov 2006 CD4 299 VL 60,000
Dec 1, Sustiva, Ziagan and 3TC
Jan 07, CD4 400

Offline bimazek

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i have been checking google almost daily for some updated news, and i have seen nothing on google about OPAL
dont be too down about kp 1461 because they may be able to come up with other versions just like azt and other drugs were nasty at first, not sure why they stoped it

Offline bimazek

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is there any one in Australia who can contact these people and find out any news

when will human trials start?
are they ready for human trials?
is there any hurdles?
how did they come up with the idea?
what are their hopes and concerns etc?

Australia 

 


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