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Studies in monkeys may be next step in search for HIV cure by powerful infusion.

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Tadeys:
(Reuters) - A powerful infusion of HIV-fighting antibodies beat back a potent form of the virus in monkeys and kept it at bay for weeks, U.S. government scientists and a team led by Harvard University found, offering a potential next step in the battle against human HIV.

The two studies, published on Wednesday in the journal Nature, involve the use of rare antibodies made by 10 percent to 20 percent of people with HIV that can neutralize a wide array of strains.

Such antibodies latch on to regions of the virus that are highly "conserved," meaning they are so critical to the virus that causes AIDS that they appear in nearly every HIV strain.

By attaching to the virus, they make it incapable of infecting other cells.

In the past decade, scientists have tried to make vaccines that could coax the body into making these same types of HIV-specific antibodies. But finding a way to make these complex antibodies has been challenging.

"These are the Ferraris of antibodies," said Dr Dan Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center and a professor at Harvard Medical School, who led the larger of the two studies.

"Nobody, including ourselves, has been able to develop a vaccine that can generate immune responses that are even close."

In the studies, the teams instead tested these antibodies as a potential treatment for people infected with HIV. Both teams used rhesus monkeys with the Simian-human immunodeficiency virus, a monkey version of HIV.

Barouch's team studied the rare antibodies harvested from HIV-infected humans that were grown in large batches and could be infused at high doses. The team tested different combinations of antibodies in 35 infected monkeys.

The one that worked best was an antibody called PGT121.

"Basically, that antibody, given either alone or in combination, resulted in a dramatic effect," Barouch said.

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The antibodies reduced the virus to undetectable levels in 16 of 18 monkeys within seven days, and kept it there for one to three months. In three animals with the lowest viral load at the time of treatment, the virus did not resurface.

A smaller study by scientists at the National Institute of Allergy and Infectious Diseases, a part of the National Institutes of Health, showed similar results.

Both teams say the approach should now be tested in people.

"All the data to date exist in the monkey model. We need to evaluate how these antibodies perform in humans infected with HIV," Barouch said.

His team did not test the antibody treatment in combination with antiretroviral treatments, the standard HIV drugs used by thousands of patients to control the virus.

But Barouch thinks such combinations would make sense because both treatments have different mechanisms of action.

While antiretroviral drugs only attack the machinery used by the HIV virus to make copies of itself, antibodies can directly attack free virus particles in the blood as well as in cells that are infected with the virus.

Barouch said researchers and drug companies are interested in the results, which could offer a next step toward a cure for the infection that causes AIDS.

In an interview on the Nature website, Dr Louis Picker of Oregon Health & Science University, who wrote a commentary on the research, said the study is "a baby step towards cure."

He said antiretroviral treatments, such as those made by Gilead Sciences and GlaxoSmithKline, reduce the ability of the HIV virus to replicate in the body by maybe 99.9 percent, but not 100 percent.

"This treatment on top of it may bring it to 100 percent," he said.

Still unclear is whether antibodies will also attack latent HIV cells that hide in the body and allow the virus to reappear when treatment stops.

"We haven't shown any cures," Barouch said. "However, we have shown the antibodies act not only on the virus in the bloodstream, but can also substantially reduce virus in tissues such as lymph nodes and the gut. Future research with these antibodies will help determine whether they might be part of a virus eradication or cure strategy."

http://www.reuters.com/article/2013/10/30/us-hiv-antibodies-cure-idUSBRE99T1B820131030


Tadeys:
"In three animals with the lowest viral load at the time of treatment, the virus did not resurface."

GoForIt:
This sounds very promising.  Harvard....antibodies that can get into lymph-nodes....

I like this article.

Tadeys:
This is very big. A big piece of the puzzle. More info:

Antibodies derived from the blood of HIV-infected people suppressed the virus in the blood of monkeys in two studies that suggest the experimental approach may improve AIDS therapy or point the way toward a cure.

One study showed that a single injection of antibodies reduced the simian, or monkey, version of HIV to undetectable levels in three to seven days -- much faster than regular AIDS drugs -- and the effect lasted for almost TWO MONTHS. The research, led by Dan Barouch, professor of medicine at Harvard Medical School, is published today online by the journal Nature.

The antibodies represent a new and potentially more powerful approach to treating a disease currently controlled by daily pills such as those made by Gilead Sciences Inc. (GILD) While those drugs have transformed HIV from a death sentence into a manageable disease, they don’t completely clear the virus from the body. The new antibodies attack HIV in areas the drugs don’t reach, suggesting they may have a role in curing a disease that has confounded scientists for 30 years.

“The antibodies themselves are very, very special,” said Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center, a Harvard affiliate in Boston. “These antibodies should be explored for a variety of different clinical applications. Clearly where there’s going to be substantial interest is evaluating their potential role in cure.”


http://www.bloomberg.com/news/2013-10-30/research-for-aids-cure-advances-as-hiv-fought-in-monkeys.html


geobee:
Hey Tadeys,

Thank you for posting this!  Great stuff.  Seems like you could stay on the ARVs to stop replication, then use these ABs to blast away at the reservoirs. 

It's not unlike Picker's approach with the modified CMV -- use that to constantly get the body to create antibodies.  Seems like this method is better for giving you the best type of antibody tho.  Very interesting!

Here's one of the studies:
http://www.nature.com/nature/journal/vaop/ncurrent/full/nature12744.html

"Abstract

Human immunodeficiency virus type 1 (HIV-1)-specific monoclonal antibodies with extraordinary potency and breadth have recently been described. In humanized mice, combinations of monoclonal antibodies have been shown to suppress viraemia, but the therapeutic potential of these monoclonal antibodies has not yet been evaluated in primates with an intact immune system. Here we show that administration of a cocktail of HIV-1-specific monoclonal antibodies, as well as the single glycan-dependent monoclonal antibody PGT121, resulted in a rapid and precipitous decline of plasma viraemia to undetectable levels in rhesus monkeys chronically infected with the pathogenic simian–human immunodeficiency virus SHIV-SF162P3. A single monoclonal antibody infusion afforded up to a 3.1 log decline of plasma viral RNA in 7 days and also reduced proviral DNA in peripheral blood, gastrointestinal mucosa and lymph nodes without the development of viral resistance. Moreover, after monoclonal antibody administration, host Gag-specific T-lymphocyte responses showed improved functionality. Virus rebounded in most animals after a median of 56 days when serum monoclonal antibody titres had declined to undetectable levels, although, notably, a subset of animals maintained long-term virological control in the absence of further monoclonal antibody infusions. These data demonstrate a profound therapeutic effect of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys as well as an impact on host immune responses. Our findings strongly encourage the investigation of monoclonal antibody therapy for HIV-1 in humans."

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