POZ Community Forums
Meds, Mind, Body & Benefits => Research News & Studies => Topic started by: xxname on January 03, 2008, 03:19:32 pm
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Researcher of the Month - November 1, 2007
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Dr. Yong Kang
University of Western Ontario
A Two-Decade Quest to End Aids
“This vaccine has the potential of saving millions of lives,” says Yong Kang, a professor of Microbiology and Immunology in the Schulich School of Medicine & Dentistry at The University of Western Ontario. It’s always wise to have realistic expectations, but Kang hopes he is closer to finding a cure for HIV/AIDS – and he’s already much nearer to succeeding than most have ever been.
The AIDS pandemic has killed more than 25 million people and infected 40 million more since the virus was first discovered in 1981, and experts say a viable vaccine is the best hope of ending the tragedy. Kang's tireless quest to develop a vaccine against HIV/AIDS has spanned nearly two decades and has just entered a new phase. "The results look encouraging, and we are now moving onto pre-clinical animal toxicology trials," he says.
Kang's work has produced one of the few technologies to make it so far in a process where dozens of other potential vaccines have failed. His technology could not only produce antibodies against HIV, but also prime T-cells to destroy cells harboring the virus, essentially curing a patient with HIV infection.
"We created a genetically modified HIV and recombinant human adenoviruses to develop a vaccine which can prevent HIV infection and clear HIV-infected cells. It can produce antibodies against HIV and educate one type of white blood cells to find infected cells and kill them," explains Kang. "We hope the vaccine will not only prevent HIV infection, but that it can be used as an immuno-therapeutic agent."
With the help of Western’s Industry Liaison office, Kang licensed his inventions to Curocom, a publicly traded holding company in Korea. Curocom is sponsoring research in Kang's lab and recently opened a subsidiary office at Western’s Research Park to accelerate aspects of the commercialization process of the HIV vaccine program.
Kang’s vaccine is currently being manufactured in a Maryland laboratory in anticipation of FDA approval to continue with Phase 1 and 2 human clinical trials. His vaccine could be available for therapeutic use within three years and for use as a preventive vaccine within the next six years(?????????). (IS TRUE?????????????)
Kang was educated in Korea and Denmark for his undergraduate[/b] studies, received his Ph.D. from McMaster University, D.Sc. from Carleton University and did his postdoctoral training at the University of Wisconsin, Madison. He taught at the University of Texas and the University of Ottawa, before coming to The University of Western Ontario as the Dean of Science in 1992.
For further information, please contact Dr. Yong Kang at 519-661-3226 or cykang@uwo.ca
http://www.chrcrm.org/main/modules/pageworks/index.php?page=002&id=565
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It's another overly zealous press release designed to inflate the stock price of the companies named within. No researcher worth his salt would make such pronouncements before the approval of even Phase 1 trials in humans.
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The results look encouraging
How many thimes have we heard this, and how many times have we been let down..but I like to keep an open mind, so we can only wait and see.
But I have to agree with this
Posted on: Today at 08:56:47 amPosted by: redhotmuslbear
Insert Quote
It's another overly zealous press release designed to inflate the stock price of the companies named within. No researcher worth his salt would make such pronouncements before the approval of even Phase 1 trials in humans
Hugs
Jan
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This has been discussed extensively in other threads. I would be interested to see if/when any news comes out about the potential upcoming US trials...but I haven't heard anything yet.
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Had a look on the Western Ontario website....did find Dr Yang but nowhere did i find any mention of HIV Vaccine work, no news or anything...very strange..would of thought they would of said something about it....If anyone else can find any mention of it on their website, do let us all know.
Cheers,
Mark86
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Here are some references to Dr. Kang and his research on the UWO website:
http://www.google.com/search?q=hiv+vaccine+kang&as_sitesearch=uwo.ca
Nothing earth-shattering, but apparently the research is going on, with UWO acknowledging it.
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Yes this has been discussed in other threads.
Last I heard they (Dr. Kang and Curocom, the Korean company financing the trials) were waiting for the final FDA approval to start phase 1.
At least the Korean company has significant faith in the vaccine technology Dr. Kang has developed, given that they are providing $50 million dollars to test the vaccine. Let's hope for the best.
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His vaccine could be available for therapeutic use within three years and for use as a preventive vaccine within the next six years(?????????). (IS TRUE?????????????)
eer, actually available in 2 yrs now according to this 2006 article!
http://www.canadian-universities.net/News/Press-Releases/October_17_2006_CLINICAL_TRIALS_NEXT_FOR_HIV-AIDS_VACCINE_KOREAN_B.html (http://www.canadian-universities.net/News/Press-Releases/October_17_2006_CLINICAL_TRIALS_NEXT_FOR_HIV-AIDS_VACCINE_KOREAN_B.html)
If its actually true, I hope the powers that be dont sit on it!
Denniss
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How many thimes have we heard this, and how many times have we been let down..but I like to keep an open mind, so we can only wait and see.
But I have to agree with this
Hugs
Jan
Annie as the Global Moderator Member I dont see how this kind of fatalistic negative hopeless post does any good and perhaps you could speak for yourself, as "I" not we, and why as someone who i am assuming is on haart, which was created by hard work of scientists are you not reverent and respectful of the very hard work of millions of underpaid researchers including this one
How many thimes have i heard this, and how many times have i been let down
this is great great progress being made
they are almost at a solution
there are 150 new meds in the pipeline according to the latest issue of poz mag or in trials
they are coming up, in trials, with new non nukes that dont cause the bad dreams and neuro effects
etc
we --- and perhaps i should say all of you who are on meds, because i am not on them yet, but i will if i get to 350 t cells
"we" should all be bowing down to science for keeping us alive
and
respect the hard work of researchers all over the world
i also disagree with the idea that companies post announcements to get the stock price up
they have to be extremely careful what and when they do any press release if they are a real company
and they deserve to have freedom of speech
happy new year
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I strongly agree, hope is what keeps me living
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I also agree. The one I've focused on is the Koronis trial. Even if it might be a "let down" in the end, it will serve a purpose to get me through yet another year... and then on to the next great hope. One of these days, one of them will actually come through. Look how long it took the integrase inhibitors to finally come to be... and look how potent Isentress seems to be. I'm also still waiting for the Ensoli vaccine trials to start again.
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Interesting point about the Ensoli trials....
I had a quick google and it seems Phase 1 finished a few years ago. The only reference to it i could find was..
AIDS. 2006 Nov 28;20(18):2245-61.Related Articles, Links
Candidate HIV-1 Tat vaccine development: from basic science to clinical trials.
Ensoli B, Fiorelli V, Ensoli F, Cafaro A, Titti F, Buttò S, Monini P, Magnani M, Caputo A, Garaci E.
but there was no abstract i could read. Is this still moving forward or are there problems ???
Hope its still ok though...
Mark86
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Biz, while I generally agree with what you are saying and am 100% a fan of scientific research, there is no denying that public companies are beholden to stock holders and are from time to time guilty of timing certain announcements in relation to stock price.
As for Ensoli - what the hell happened to that thing? From what I was reading on the 'old' forum, there were supposedly people who had stopped meds and continued to have undetectable vl. Yet I can't find anything about it now except references to law suits over who discovered what, ect, ect. What a dissapointment. At one point, there was an activist from Italy who posted here a few times to let us know what was happening over there, but I haven't heard from him in a while.
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ah, the famous Ensoli trials...
Well, it appears that they turned into something resembling an Italian soap opera with egos bruised and reputations tarnished when one of Ensoli's former cronies criticized her research. Where did this end up? In court.
Here's some coverage of the mess:
http://news.xinhuanet.com/english/2007-08/13/content_6520455.htm
(I had my eye on this vaccine too. At least there are more strategies in the pipeline.)
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So annoying. How about taking the money from the friggin lawsuits and putting it into trials? Are the trials actually going on? What about the people who already got the vaccine - surely someone must be following them. I still don't see any mention of any of that anywhere. What a waste.
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Well according to the article linked by Jake the second phase did begin, and should take 2-3 years. If true, this could conceivably explain the lack of news, since no researcher will comment on a particular phase until the moment it ends and data analyzed. Fingers crossed, I guess.
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Any news about dr Kang from University of Western Ontario(Canada)?
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xxname,
I've merged your new thread on the subject of Dr. Kang with the one you started on the same subject back in January. I also changed the thread's title so people can know at a glance what the thread is about. I would appreciate it if you'd make the subject of your thread clear in the title in future.
I'd also appreciate it if you would keep subjects in one thread, instead of starting new threads on subjects with an already existing thread. If you need help finding your thread when you come here, click on the "Show own posts" link under your name in the left-hand column of any forum page.
Please also read through the Welcome Thread (http://forums.poz.com/index.php?topic=11292.0) so you can familiarize yourself with our Forum Posting Guidelines.
Thank you for your cooperation.
Ann
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Any news about dr Kang from University of Western Ontario(Canada)?
He's working as a clown in a circus, together with many other "HIV/AIDS researchers".
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LoL Leit..... ;D
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Hopefully that clown will fool us all and find a cure. ;D
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Here's an update from Canwest news service in Canada and the University of Western Ontario website....perhaps some hope!!!!
www.canada.com/calgaryherald/news/story.html?id=33b166b1-369f-48da-8c48-0ab816bca3d3
communications.uwo.ca/com/western_news/stories/western_proposes_first_hiv_vaccine_facility_20081112443163/
(might have to copy and paste these)
Cheers!!
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Finally some news!!!! I have great hopes for this vaccine.
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Guys, guys...am I missing something here? I'm as optimistic as the next person, most likely more so. The continuing advances in gene related therapies, monoclonal antibodies, etc, are very exciting. But this? I've read the press releases from Dr Kang and am left asking each and every time, "where's the beef?". To be nice, it sounds like a bunch of overhyped bs. Endless delays, no human trials, no peer review, and classic over promising / under delivering. Hmmm...
This appears to be the Sarah Palin of HIV treatments.
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I have to admit, I've been watching this one from day one and they keep promising big things and then we hear nothing.. I thought it was further along also, but at least something is happening finally.
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:::sigh:::
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Wow...Dr. Kang's "miracle" cure really is like Sarah Palin...a seemingly worthless POS that won't go away :o
C'mon guys, this thing is a joke.
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This is the latest news about Dr. Yong Kang.
http://communications.uwo.ca/com/western_news/stories/western_proposes_hiv%10aids_vaccine_facility_20081112443158/
:)
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Here's some more details on the progress of the vaccine itself. As you can see it's moving ahead, these things just take time.
From http://www.physorg.com/news145722346.html
(PhysOrg.com) November 12, 2008 -- The advance towards a vaccine for HIV/AIDS has taken another step closer to realization. A vaccine, developed by Dr. Chil-Yong Kang and his team at the Schulich School of Medicine & Dentistry at The University of Western Ontario, and licensed to Sumagen Canada Inc., has now been manufactured for use in trials - first, in toxicology trials using animal models and then in Phase 1 human clinical trials.
The vaccine has been manufactured at a bio-safety level 3 (BSL3) good manufacturing practice (GMP) facility in the United States.
“It has been very difficult to manufacture our genetically engineered HIV-1 experimental vaccine, because there are only a few BSL3 GMP contract manufacturing organizations (CMO) available in the world. For this reason, we welcome the Canadian Government’s plan to establish a BSL3 GMP facility in Canada for future manufacture of candidate HIV/AIDS vaccines. We have overcome a major hurdle in the development of our HIV/AIDS vaccine which is now ready for clinical trials,” said Dr. Dong Joon Kim, CEO of Sumagen.
The toxicology trials will get under way in a matter of days at a contract research organization (CRO) in the U.S., and results should be ready in approximately three months. The Phase 1 human clinical trials could begin in early spring at a number of trial sites in North America.
Kang's vaccine uses a killed whole HIV-1, much like Salk's killed whole poliovirus vaccine. The HIV-1 is genetically engineered in such a way that it is non-pathogenic and can be produced in large quantities. It is then purified, inactivated, and injected as a safe whole killed-virus vaccine.
While Phase 1 human clinical trials are most often conducted on healthy volunteers, in the case of this HIV/AIDS vaccine, it will be tested on individuals who are HIV-positive, but not yet symptomatic with AIDS.
More than 25 million people have died of AIDS since 1981 and approximately 35 million people live with HIV infection world-wide today.
Sumagen Canada Inc. is a subsidiary of Curocom of Korea. The company is fully funding Dr. Kang’s continuing work on the HIV/AIDS vaccine development.
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Another article, http://pharmalicensing.com/public/press/view/1227541478_492acbe6d4440/will-a-new-approach-create-cure-for-hiv .
By Paul Mayne Thursday, November 20, 2008
After more than 20 years of labouring on an HIV/AIDS vaccine, Yong Kang’s research has reached an historic moment.
The professor in the Schulich School of Medicine & Dentistry’s Department of Immunology & Microbiology is excited to see his vaccine enter an important testing phase this month in the United States.
If the initial toxicology tests prove successful, phase 1 human clinical trials could begin as early as three months from now at a number of sites in North America involving HIV positive individuals not yet symptomatic with AIDS.
“We have been working on this project for over 20 years,” says Kang.
“It has been a long, painful process, but we have gotten to this stage now, to test our vaccine, and see whether or not it can prevent HIV infections. Despite the tremendous amount of scientists working on this project, to date there has not been an effective vaccine.”
Kang and his team have invested years getting to this point; even so, they are certainly not alone in having created a vaccine that could potentially curb the deadly toll of this virus.
According to the HIV Vaccine Trial Network, there are 13 ongoing clinical trials, each representing years of work and countless dead ends, each approaching the potential solution in a different way, and each representing hope.
“Over the 20-year period there has been some ups and downs because of the failure of some of the well-known trials, therefore when we see that kind of failure we are discouraged. However our strategy is not the same as the others, so in some way we are encouraged to see whether our vaccine strategy will work better,” says Kang.
The genetically engineered vaccine, produced in large quantities in a Maryland lab, uses what he calls a killed whole HIV-1. The idea is the vaccine would prime T-cells to destroy cells harboring HIV, essentially curing a patient of the virus.
The vaccine is licensed to Sumagen Canada Inc, a subsidiary of Curocom of Korea, which is fully funding Kang’s work on the vaccine.
“I really hope for the success of our vaccine, not just for our company and The University of Western Ontario, but for all humankind,” says Dong Joon Kim, CEO of Sumagen.
Ted Hewitt, Western’s Vice-President (Research and International Relations), says after a long and intensive process, Kang has been issued one of only a very few HIV vaccine patents in the world.
“He has developed the technology to take it this far in a process where dozens of other potential vaccines, from much larger institutions globally have failed,” says Hewitt. “We are tremendously proud of Dr. Kang’s accomplishments to this point.”
Kang says while he sees the trials of fellow scientists worldwide fail, which he admits can be discouraging, he is confident his approach to the vaccine is a step others have not taken.
“It has been a tremendous effort to engineer or design a vaccine,” says Kang, adding “this type of research and development is so important for humankind to saving millions of lives.”
“The success of this vaccine will really help the millions and millions of people around the world affected by HIV/AIDS,” says Kang, noting the AIDS pandemic has killed 25 million people and infected 40 million more. “We can save lives around the world. This is a very important step.”
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Wow...great "update", i.e. more of the same.
J220, all due respect, but why do you keep posting essentially the same article for this untested, non peer reviewed, overly hyped, "cure"? As no doubt you've read, there has yet to be even the most preliminary phase 1 testing (let alone phases 2 & 3). There has been no peer review of any sort - only hyperbole and hype ("historic moment", "cure". "all humankind", etc). Does it not seem curious that the only people commenting on and hyping this "cure" and approach are those with a financial interest in it?
Evidently you've become emotionally invested in this quackery for some reason. Good luck with that.
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freewillie99 this world can be a better place. Try to contribute positively.
"historic moment", "cure". "all humankind"
what do you want instead ? depression, suicide, cry
Do it for yourself if it is your way to live with this disease
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what do you want instead ? depression, suicide, cry
No, John, I prefer "peer reviewed", "tested", "proven". Much better.
Your response was predictable and humorous.
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Wow...great "update", i.e. more of the same.
J220, all due respect, but why do you keep posting essentially the same article for this untested, non peer reviewed, overly hyped, "cure"? As no doubt you've read, there has yet to be even the most preliminary phase 1 testing (let alone phases 2 & 3). There has been no peer review of any sort - only hyperbole and hype ("historic moment", "cure". "all humankind", etc). Does it not seem curious that the only people commenting on and hyping this "cure" and approach are those with a financial interest in it?
Evidently you've become emotionally invested in this quackery for some reason. Good luck with that.
The articles do contain new and relevant information, whether you agree or believe in it or not (and no one is asking you to, nor am I interested in your laughable assessment of my emotional landscape). You are under no obligation to read the articles, nor any of my posts, so feel free to ignore them.
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freewillie99 this world can be a better place. Try to contribute positively.
It is indeed a positive act to debunk false information and those who disseminate it. It is cruelty to stand by and watch people duped by frauds and follow fraudulent leads to nowhere.
Think of the energy wasted on unworkable methodology, and unscrupulous persons who profit on the desperate and gullible.
IMHO, I think those who spend their time following false leads to "cures" would have better luck petitioning their elected officials to allow the meds currently on the market to be distributed to those who need them, regardless of cost.
And to insist on first-tiered peer review is NOT an unreasonable request. It is the process by which scientific advancement occurs.
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Oh, the drama! Can we just post info about the Kang vaccine here without all the high jinks? Sorry to be a prisspot but not all of us have all day to wade through endless minor offenses and comebacks just to see the latest info someone has found (thanks J220!).
Sorry guys, just in a no-BS mood today :o
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Oh, the drama! Can we just post info about the Kang vaccine here without all the high jinks? Sorry to be a prisspot but not all of us have all day to wade through endless minor offenses and comebacks just to see the latest info someone has found (thanks J220!).
Sorry guys, just in a no-BS mood today :o
In other words, no mood to have a paradigm questioned? Seriously, debating on the ethics and merits of a scientist is hardly a "hijink."
Unless the search for scientific accuracy and veracity is not the perview of this forum.
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Oh, the drama! Can we just post info about the Kang vaccine here without all the high jinks?
Ok, NYCguy, point taken. I'll look forward to your next posts on the latest breaking colloidal silver and enema therapy press releases.
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It is indeed a positive act to debunk false information and those who disseminate it. It is cruelty to stand by and watch people duped by frauds and follow fraudulent leads to nowhere.
Think of the energy wasted on unworkable methodology, and unscrupulous persons who profit on the desperate and gullible.
You're absolutely right, "jkinatl2"! Decades of broken promises only transformed my hopes into despair.
Dear newly infected friends, please don't waste too much hope before successful IIb phases!
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First of all, everyone please watch the snarkiness and defensiveness. Neither are particularly helpful.
To be honest, it is difficult to have a "scientific dialogue" about this particular vaccine, because there has been so little data published in a journal or at a conference. One could argue the theoreticals, but that's about it at this point. If some people choose to place their faith in this vaccine and are later disappointed, then that's their right. We've all been there at some point.
Why don't we all hold our breath and our tempers until more data are published. I don't even need to see phase IIb studies, but I do want to see a full immunologic panel from subjects who are immunized with the vaccine. I also want to see what their plans are for dealing with the adenovirus vector. This is the same type of vaccine delivery device that may have led to problems in the STEP vaccine trial, and there are now safety concerns that must be contended with.
Respectfully,
David
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It is hard not to be skeptical, in light of so many promises and subsequent failures... I do know, however, that Dr. Kang is considered one of the leading virologists in Canada and his work his highly regarded. Let's hope he lives up to his reputation...
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Couldn't agree more...the vaccine may yet fail, but a quack he ain't.
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Moving on to the subject of the thread, I found an interview of Dr. Kang by Steve Paikin where he talks about his vaccine efforts:
Part 1: http://www.youtube.com/watch?v=86SakgTdiIM
Part 2: http://www.youtube.com/watch?v=5ocJMzP8RRA
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Hi-
I have not checked this site for over a year. I thank everyone who
helped me during my HIV scare when I needed it the most.
It is interesting how little this study is being recognized.
When I lived in Toronto, I met a person whose father is a colleague of Dr.Kang.
He told me the University was always very optimistic over Dr.Kang's research and believe
now with the relationship with the Government of Canada and CURACOM that
this vaccine is looking very positive and a true reality.
Best
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UWO-developed AIDS drug ready for human tests
Wed, March 18, 2009 •
By JOHN MINER
An HIV/AIDS vaccine developed at the University of Western Ontario has successfully completed toxicology tests on animals, opening the door to tests on humans. "We're one more step closer," said Dr. Chil-Yong Kang, who developed the vaccine with his team at the Schulich School of Medicine and Dentistry over the past 20 years.Western holds the patent on the vaccine that it has licensed to Sumagen, a South Korean pharmaceutical company.Within the next few months, Sumagen is expected to apply to the U.S. Food and Drug Administration to carry out toxicology tests on about 35 people. The tests will be done in the U.S."It won't take any more than six months," said Kang.
If the vaccine clears that hurdle, then it will move to what is called phase 2 clinical trials, testing the immune response in 600 to 700 volunteers.That will likely take a little more than a year, Kang said.The final phase, if no problems are discovered with the vaccine, will involve thousands of people and test if the vaccine can actually prevent infection by the virus.Unlike other HIV/AIDS vaccines that have been developed using fragments of the virus, Kang's uses whole killed virus, the same approach that is used for vaccines against influenza.The UWO scientists genetically engineered the virus used in the vaccine so it was no longer dangerous and could be produced in large quantities.
John Miner is a Free Press health reporter.JOHN.MINER@SUNMEDIA.CA
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"We're one more step closer," said Dr. Chil-Yong Kang
zzzzzzzzzzzzzzzzzzzzzzzzzzzz....................
wake me up when dr. kang's "one more year" is over.
[attachment deleted by admin]
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xxname: Thanks for the update on what stage this is in. It's very good news that they've successfully completed animal toxicology tests.
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When the clinical trials start, the efficacy of a therapeutic vaccine should be obvious fairly quickly. What will take time is the safety studies. The vaccine must be proven safe over time. Unfortunately there is no animal model hiv that reacts the same way hiv reacts in humans as the good doctor said. So going after latent cells will be the big issue for eradication.
Lets hope for the best
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Unfortunately there is no animal model hiv that reacts the same way hiv reacts in humans as the good doctor said.
V:
Did you miss this?
http://blog.wired.com/wiredscience/2009/03/monkeyhivmodel.html
HIV Hack Lets Scientists Study Human AIDS in Monkeys
A genetically engineered strain of HIV will allow scientists to study a human version of the disease in monkeys. Until now, AIDS researchers used monkeys infected with simian immunodeficiency virus, or SIV. The virus is similar to ours, but it's far from a perfect research tool. "The lack of a primate model that utilizes HIV-1" — the strain that causes human AIDS — "is an impediment to research," write researchers led by Paul Bieniasz and Theodora Hatziioannou of the Aaron Diamond AIDS Research Center.
The new HIV strain, described Monday in the Proceedings of the National Academy of Sciences, could eventually make it easier to test drugs and vaccines for the incurable virus.
Though SIV and HIV wreak similar havoc on their hosts' immune systems, drugs affect them differently. While that makes SIV useful for studying how the disease progresses, it's less useful for studying potential treatments. It's impossible to quantify how much this has slowed the search for cures to a disease that kills nearly three million people every year, but it certainly hasn't helped.
Carolyn Williamson, principal investigator of the South African AIDS Vaccine Initiative, said that existing monkey models are "not ideal" for testing vaccines and drugs. She was not involved in the study.
"This model is a real step forward in HIV research," said Williamson. Monkey immune systems normally beat back HIV with the help of two cellular proteins that prevent retroviruses from replicating.
Pigtail macaques, however, lack a gene variant that codes for one of those proteins. By swapping a key gene from SIV into HIV, the researchers produced a strain that evaded the other protein defense.
When the macaques were infected with the engineered HIV, the virus developed slowly, at rates comparable to humans who keep the disease at bay for decades. "If your drug was developed for HIV-1, it doesn't necessarily work for monkey viruses," said Hatziioannou. "In this model, you know it's going to work the same way as in humans."Researchers will be able to study the mechanisms of so-called long-term non-progression — and that's just the start. The next step, said Bieniasz, is the development of an HIV strain that produces full-blown AIDS in the macaques, allowing researchers to test treatments for that stage of the disease.
Citation: "A macaque model of HIV-1 infection." Theodora Hatziioannnou, Zandrea Ambrose, Nancy P.Y. Chung, Michael Piatak, Jr., Fang Yuan, Charles M. Trubey, Vicky Coalter, Rebecca Kiser, Doug Schneider, Jeremy Smedley, Rhonda Pung, Mercy Gathuka, Jacob D. Estes, Ronald S. Veazey, Vineet N. KewalRamani, Jeffrey D. Lifson, and Paul D. Bieniasz. Proceedings of the National Academy of Sciences, Vol. 106, No. 9.
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Re: animal models, there's also this, it's not a done-deal but they seem to be getting there:
http://www.drugdiscoverynews.com/index.php?newsarticle=2385
Of Mice and HIV Models
2008 September
by Jeffrey Bouley
Cell
Harvard University Medical School
Jackson Laboratory
University of Massachusetts
Email the author
CAMBRIDGE, Mass.—The good news coming from a recent study published in the Aug. 22 issue of Cell is that small interfering RNA (siRNA) delivered directly to immune cells can suppress the human immunodeficiency virus in animal models of the disease. Perhaps the better news, using a long-view perspective, is researchers are finally zeroing in on making the animal models for HIV better—particularly in the challenging realm of making good HIV mouse models.
The authors of the paper, “T Cell-Specific siRNA Delivery Suppresses HIV-1 Infection in Humanized Mice,” noted that along with the enduring problem of finding an effective strategy for delivering siRNA to the proper site in real-life systems, they have been stymied in the past by a lack of appropriate HIV animal models.
“Animal models for HIV-1 have suffered from either the lack of a system that precisely mirrors human HIV infection or, in the case of primate models, scarcity of species, high cost, and the need to use the related but distinct simian virus for infection,” noted the authors.
Lead author Dr. Priti Kumar, an instructor and post-doctoral research fellow at Harvard University Medical School’s Immune Disease Institute and Department of Pediatrics, adds that to overcome the animal model problem, several labs have been working on immuno-deficient mice that can be transfused with human T-cells and/or stem cells. For her study, the researchers used a new mouse strain, developed by co-authors Dr. Leonard Shultz, a researcher at the Jackson Laboratory, and University of Massachusetts researcher Dr. Dale Greiner, that can be transplanted with human immune cells or human stem cells that subsequently generate a human immune system in the animals.
“The key advance we achieved is that for the first time, these mice develop a complete functional human immune system including robust development of the cell target of HIV, CD4 T cells,” Greiner explains. “Previous mouse models used for HIV failed to reproducibly develop CD4 T cells following hematopoietic stem cell engraftment.”
“We built on a lot of earlier work that had helped produce mice with deficiencies that allowed us to more closely humanize them and overcome the innate immune system, a much more ancient kind of immune system that had tended to thwart our ability to make models that accurately predict human responses,” Shultz says.
Earlier mouse models that lacked or had sharply deficient innate immune systems—though they were the gold standard for HIV and other research efforts for many years—still resisted engraftment, and the model that he and Greiner helped develop supports the higher level of engraftment that Kumar and her colleagues needed for the siRNA research.
More work is needed to get the mouse models perfected, Shultz and Greiner acknowledge, with Shultz calling humanized mice “a moving target that is always going to need improvement.”
“The major advances needed are development of immunodeficient mouse models expressing human HLA molecules to permit appropriate T cell development,” Greiner notes. “Expression of human species-specific soluble factors that are needed for robust human immune system development are also needed to enhance human immune system development in the immunodeficient mice further.”
As for the original point of Kumar’s research using the newer mouse model, her team demonstrated that they could thwart HIV in mice by delivering interfering RNAs to T-cells. By silencing three genes, the team protected these cells from much of the damage typically associated with HIV infection, a sign of hope that researchers might come up with effective siRNA-based HIV therapies for humans.
Because T-Cells are recalcitrant in the uptake of nucleic acids, Kumar and her team “coaxed” them to take up the molecules by attaching them to an antibody against a T-cell surface protein.
But even with a solution to that problem, they had to overcome rapid viral mutation. To reduce the problem, the researchers targeted three different sequences: the sequences coding for CCR5, a human T-cell surface protein used by HIV to enter the cells, and two well-conserved HIV proteins.
The antibody-siRNA cocktail they administered to treat immune-deficient mice containing HIV-negative human T-cells gave them dramatic results. The control mice and mice who were given other siRNAs lost T-cells as soon as ten days following HIV infection, while roughly 75 percent of the mice given the therapeutic siRNAs had T-cell profiles that were essentially like those of non-HIV mice. DDN
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Damn Free and Inch you guys are good. I stand corrected. Perhaps that will teach me to quote a researcher without doing my own homework.
Who knows, maybe if we all do enough research we can connect the dots to a cure. (LOL).
Thanks for the links!
V
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The animal tests are completed and the vaccine is ready for trial:
"Omnia Biologics, Inc. and Sumagen Co., Ltd. jointly announced the successful completion of cGMP manufacture of Sumagen's HIV/AIDS vaccine for a Phase I clinical trial.
Sumagen, like many companies in the experimental biologics space, has had great difficulty in finding suitable contract manufacturing expertise to move their products into clinical trials. After the failure of other CMOs, we are happy that Omnia's customer focused and product specialized services were able to satisfy 250% of their required yield on schedule." (Omnia Biologics)
The Korean Company will pay all trials and Chil-Yong Kang made an agreement that the vaccine will be free to the African people and available at an affordable price for others.
I hope they are successfull and dont get a problem with this Adenovector.
http://www.wipo.int/pctdb/en/fetch.jsp?LANG=ENG&DBSELECT=PCT&SERVER_TYPE=19-10&SORT=41268291-KEY&TYPE_FIELD=256&IDB=0&IDOC=1613154&C=10&ELEMENT_SET=FILENAME,IMAGEROOT-ENG&RESULT=1&TOTAL=1&START=1&DISP=25&FORM=SEP-0/HITNUM,B-ENG,DP,MC,AN,PA,ABSUM-ENG&SEARCH_IA=IB2008000668&QUERY=%28WO%2fWO%2f2008%2f099284%29+ (http://www.wipo.int/pctdb/en/fetch.jsp?LANG=ENG&DBSELECT=PCT&SERVER_TYPE=19-10&SORT=41268291-KEY&TYPE_FIELD=256&IDB=0&IDOC=1613154&C=10&ELEMENT_SET=FILENAME,IMAGEROOT-ENG&RESULT=1&TOTAL=1&START=1&DISP=25&FORM=SEP-0/HITNUM,B-ENG,DP,MC,AN,PA,ABSUM-ENG&SEARCH_IA=IB2008000668&QUERY=%28WO%2fWO%2f2008%2f099284%29+)
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Montagnier and Erwann Loret finally want to test the TAT OYI Vaccine. There is a thread about this special TAT OYI from Gabon that makes you seronegative, here in the forum. So far the Ensoli TAT trial is running in Italy with 128 positive participants. Tat- a neverending story for more than 10 years.
http://www.laprovence.com/articles/2008/10/07/586310-France-Deux-Nobel-francais-contre-le-sida.php (http://www.laprovence.com/articles/2008/10/07/586310-France-Deux-Nobel-francais-contre-le-sida.php)
http://www.freepatentsonline.com/y2005/0106161.html (http://www.freepatentsonline.com/y2005/0106161.html)[/urhttp://www.iavireport.org/Issues/1299/vol4no5.pdf (http://www.iavireport.org/Issues/1299/vol4no5.pdf)
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HIV vaccine makers ready for human testing
Updated Wed. Jul. 1 2009 11:37 AM ET
CTV.ca News Staff
An experimental HIV vaccine developed by an Ontario researcher may soon be approved for human testing in the United States.
The vaccine was developed by University of Western Ontario professor Dr. Chil-Yong Kang, who is being supported by Sumagen Canada Inc.
The makers of the vaccine -- dubbed SAV001-H -- have sought an application from the U.S. Food and Drug Administration to begin human testing.
According to Sumagen Canada, the vaccine has already been tested on animals, without any identified adverse effects or safety risks.
It has already been patented in more than 70 countries around the world.
If approved, the human testing for the vaccine will have two phases: The first will test its safety, the second will test how much of an immune response that the vaccine stimulates.
Sumagen Canada, which is a subsidiary of a Korean drug research company, says it is prepared to start a clinical trial for the vaccine as soon as the FDA gives its approval.
To date, no cure has been found for HIV/AIDS despite years of research. The most recent clinical trials for other vaccines have been unsuccessful.
In December, Nobel Prize winner Luc Montagnier predicted that is "a matter of four to five years" before an HIV vaccine is developed.
Montagnier was one of two scientists to discover the HIV virus in 1983.
He was awarded the 2008 Nobel Prize in medicine last October.
LINKS:
http://www.ctv.ca/servlet/ArticleNews/story/CTVNews/20090701/hiv_vaccine_090701/20090701?hub=Health
http://www.upi.com/Science_News/2009/07/01/Human-trials-sought-for-AIDS-vaccine/UPI-97021246470243/
http://communications.uwo.ca/com/western_news/stories/hiv%10aids_vaccine_reaches_milestone_20090702444563/
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Sorry, but I'm not entirely clear on whether this is a therapeutic or a preventive vaccine. I saw upthread that it may be used for both purposes. Does anyone know more about the nature of the vaccine Dr. Kang's developing?
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Sorry, but I'm not entirely clear on whether this is a therapeutic or a preventive vaccine. I saw upthread that it may be used for both purposes. Does anyone know more about the nature of the vaccine Dr. Kang's developing?
It is believed it will work as both preventive and therapeutic. In the two clips from youtube provided by J220 above, Dr. Kang is interviewed and explains some of it. He mentions that they will be looking for people who are HIV+ with more than 500 CD4s to test it on. That doesn't necessarily mean it will only work on those individuals but those are the ones they want to test the vaccine on, to make sure the person is immunocompetent. It's important that the immune system still be functional to the extent that it can produce the antibodies that the vaccine will presumably induce.
There's a lot of information throughout this thread that would answer more specific questions about how the vaccine works, although I must say, it sounds surprisingly "simple." Maybe the articles in mainstream publications can't get into more specifics but to say the following sounds so simple you have to wonder why nobody tried this already (i.e. use a killed whole HIV-1 virus):
Kang's vaccine uses a killed whole HIV-1, much like Salk's killed whole poliovirus vaccine. The HIV-1 is genetically engineered in such a way that it is non-pathogenic and can be produced in large quantities. It is then purified, inactivated, and injected as a safe whole killed-virus vaccine.
"We created a genetically modified HIV and recombinant human adenoviruses to develop a vaccine which can prevent HIV infection and clear HIV-infected cells. It can produce antibodies against HIV and educate one type of white blood cells to find infected cells and kill them," explains Kang. "We hope the vaccine will not only prevent HIV infection, but that it can be used as an immuno-therapeutic agent."
This is supposed to produce a strong enough immune response to not only prevent HIV but also clear it from the body of someone already infected? Kang talks about CD8 cells then "killing" the CD4s harboring HIV in those already infected. This is supposed to happen, merely by injecting whole killed virus and recombinant human adenoviruses? There must be more to it that they are not discussing in these mainstream articles but maybe not.
YOUTUBE LINKS:
Part 1: http://www.youtube.com/watch?v=86SakgTdiIM
Part 2: http://www.youtube.com/watch?v=5ocJMzP8RRA
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fingers crossed
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...as soon as the FDA gives its approval.
yes they're waiting for the pope giving his benediction
(http://foxforum.files.wordpress.com/2009/01/pope_012509_vatican.jpg?w=202&h=300)
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yes they wait for the pope giving is benediction
For now they are saying that they are expecting FDA approval in October 2009. We'll see.
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yes they're waiting for the pope giving his benediction
Is the pope working for the FDA? ;)
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I also want to see what their plans are for dealing with the adenovirus vector. This is the same type of vaccine delivery device that may have led to problems in the STEP vaccine trial, and there are now safety concerns that must be contended with.
A study just released has determined that the adenovirus vector was likely not the problem. Although they conclude that "Safety considerations, including the possibility that vector-specific cellular immunity may impact HIV-1 susceptibility, have become major concerns for the HIV-1 vaccine field," therefore "Our findings suggest a path forward for HIV-1 vaccine development by using rare serotype vectors [not typically found in the general population] that are not suppressed by high levels of baseline vector-specific neutralizing antibodies."
Insights Into Failed HIV-1 Vaccine Trial
ScienceDaily (July 22, 2009) — Following the disbandment of the STEP trial to test the efficacy of the Merck HIV-1 vaccine candidate in 2007, the leading explanation for why the vaccine was ineffective – and may have even increased susceptibility to acquiring the virus – centered on the hypothesis that high levels of baseline Ad5-specific neutralizing antibodies may have increased HIV-1 acquisition among the study subjects who received the vaccine by increasing Ad5-specific CD4+ T-cells that were susceptible to HIV-1 infection.
Now, a study by Dan Barouch, MD, PhD, and a scientific team at Beth Israel Deaconess Medical Center (BIDMC), reported in the July 20 Advance Online issue of Nature Medicine, shows this was likely not the case.
Continued....
LINK:
http://www.sciencedaily.com/releases/2009/07/090720190810.htm
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OhioGuyHere26, you are not infected with HIV so you should not be posting here.
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Ohioguy
While I'm sure you meant well I have deleted your post, we really have to stay with in the rules of the forums or chaos will start to rule..just a gentle reminder of the rules that apply to you:
■"With the exception of the “Am I Infected?” and “Off Topic” Forums, the AIDSmeds.com Forums are intended for people who have been diagnosed with HIV (or their loved ones/caregivers). If you are questioning or unaware of your HIV status, please refrain from posting messages or questions in the Forums intended for HIV-positive people".
I know you weren't asking any questions here but it still means you are not allowed to post in tihs forum..thank you for your cooperation
Jan
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why testing mice,then monkeys,then humans ? if you want to save 35 000 000 people infected !,why not monkeys then few humans and make it quicker . Or are they concerned about monkeys life so they test rats first ? i cant understand this.
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A couple years ago a company developed mice that could have their immune systems replaced by a human immune system. In fact the recent post on RNAi documents this is the approach that company is taking. Therefore, it would seem that the mice model would be a better way to assess efficacy of the drug than monkeys. However testing in monkeys might demonstrate other side-effects particular to primates.
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Mitch and sensual,
Mitch the mouse your referring to is called a scid mouse. It has an in vivo model of the human immune system which makes it possible to test drugs and viruses in an intact mammalian immune system. Pretty effective.
http://thyroid.about.com/library/immune/blimm31.htm
v
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sensual,
Are you willing to be a test subject for drugs that haven't been through some prior tests to make sure they aren't going to kill you or make you sick somehow? Where do you think these guinea pigs are going to come from? Just wondering...
Ann
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Ann am not willing to be a test subject,i am wondering why not ommit rats and start with monkeys,then humans.
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Probably because rats are inexpensive.
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Ann am not willing to be a test subject,i am wondering why not ommit rats and start with monkeys,then humans.
OK, so you want meds to be fast-tracked and not thoroughly tested before they're given to humans, but you don't want to be one of the people to take the initial risk with these shoddily tested drugs? Sheesh. ::)
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Never considered the risk that compounds are harmless for animals but are toxic for humans? There are some examples in the medical literature of this and even long term toxicities are not predictable with animal testing.
There are new testing techniques like cell cultures which are able to demonstrate in the same manner if a drug is toxic or not.
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Probably because rats are inexpensive.
So it's a matter of costs... ::) Conspiracy theorizing? Business? Profit? Costs? Mmhh. But I thought pharma companies are working not for profit but for our wellness. Confused. :-\
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A new report published in the British Medical Journal finds that using animals for drug trials often yields inaccurate results. A team of researchers from the London School of Hygiene and Tropical Medicine compared results of six animal trials to six human trials with the same drug and found that only three trial results were the same for both humans and animals. This discordance may be due to bias, random error, or the failure of animal models to adequately represent clinical disease.
The most notable example of the difference between animal and human testing came earlier this year when six men were hospitalized when a clinical trial of TeGenero’s experimental drug TGN1412 went wrong. Within hours of taking the drug TGN1412, a candidate for autoimmune and inflammatory diseases, six volunteers wound up in a London hospital suffering from severe adverse events that included organ failure. Data from animal trials of the drug did not suggest that human test subjects would have so severe a reaction.
Professor Ian Roberts, the director of the study, notes that further understanding of how drugs affect animals and humans is necessary in order to know how to test specific medicines. “The debate over this issue is really quite hysterical. At the moment, there is too much emotion and not much science,” he notes. Roberts suggests more communication between scientists conducting animal trials and those conducting human studies, which could ensure that animal trials were better designed.
Read more: http://www.fiercebiotech.com/node/4972#ixzz0X31rU6U2
Source:
http://www.fiercebiotech.com/node/4972
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xman,
The history of TGN 1412 shows that the preclinical results and animal in vivo results were not read properly. Take a little time to read the following link in it's entirety. It gives a good explanation as to what happened. But your post proves the point that for now drugs should be tested in animals before humans until they come up with another way that is proven superior.
http://en.wikipedia.org/wiki/TGN1412
TGN 1412 activated every T-cell in the body causing a cytokine storm (the body being attacked by it's own immune system causing multiple organ failure.) The hints were there in the animal studies. It was human interpretation of the data that was faulty.
v