6 million bucks 4 gene engineered vaccine

[Almost2late]

Noticed that there's been more research on vaccines/cures than on new ARV's.. Think that's a good thing.. And Bill and Melinda represent billionaires in a good way, grateful

Bill Gates Just Gave $6 Million To Genetically Engineer An HIV Vaccine

The new approach proposes injecting genes to fight HIV, bypassing our immune systems entirely. But scientists warn that when it comes to an HIV vaccine, we’re still years away.

In a bid to someday provide people with the ability to fend off HIV, the Bill & Melinda Gates Foundation awarded $5.8 million on Thursday to vaccine researchers.

A novel genetic engineering approach garnered the award for a Scripps Research Institute group in Jupiter, Florida, who hope to create the first effective HIV vaccine. HIV, the virus that causes AIDS, infects about 2 million people worldwide every year.

The key to the new approach is that technically, it isn't really a vaccine.

Rather than teach the immune system to fight HIV like a standard inoculation, the new method delivers genes into muscle cells and effectively re-engineers our bodies to fight off the virus.

In February, the group showed that these genes successfully eliminate the virus from monkeys and protect them from future infections.

"It's taking what is a basic gene therapy technology and using it to address the problem of a HIV vaccine," Michael Farzan, the professor of immunology and microbiology at Scripps who was awarded the grant, told BuzzFeed News. "We've got to think about getting away from the conventional mode of thinking about vaccines, especially when it comes to HIV."

Despite the recent promise of gene therapy, some scientists worry that a fully effective human vaccine is still many years away.

"There's no guarantee that we'll get an HIV vaccine — the jury's still out," Carl Dieffenbach, director of the division of AIDS at the National Institute of Allergy and Infectious Diseases, told BuzzFeed News.

Traditional vaccines introduce weak or dead pathogens into our bodies, training the immune system to attack the disease.
Once our immune cells learn which specific antibodies are needed to defeat a specific virus, we can be protected for long periods of time.

HIV, however, is a cunning virus. It's both incredibly diverse and mutates rapidly within our bodies. The virus also infects the very immune system that's meant to fight against it. To successfully beat the virus, our bodies need to be able to produce antibodies that can fight many strains of a constantly mutating target.

That helps explain why scientists have struggled to make an HIV vaccine for nearly 30 years. AIDS has claimed nearly 39 million lives to date, despite the discovery of treatments for infected patients in the 1990s.

In 2009, a group led by Philip Johnson at the Children's Hospital of Philadelphia discovered that gene therapy might bypass the immune system altogether to craft new kinds of HIV vaccines. Johnson figured out how to package antibody genes inside a virus, which then specifically invades muscle cells. Once inside the cells, the viruses park there, turning the muscle cells into factories to produce the desired antibodies.

Johnson's technique worked. While monkeys who had the powerful gene delivered were protected from doses of the primate version of HIV, the monkeys without it died.

A huge boost to HIV vaccine hopes came a year later, when scientists discovered antibodies more powerful than any others previously found in people. They resided in the cells of a 60-year-old black gay man known only as Donor 45. Unlike most antibodies, these so-called broadly neutralizing antibodies (BNABs) fought back against HIV, wiping out nearly 91% of its strains.

BNABs have since become the "holy grail" of HIV vaccine research, Richard Jefferys, director of basic science, vaccines, and cure projects at the Treatment Action Group, told BuzzFeed News.

Many researchers have been trying to figure out how to coax our immune systems to produce BNABs on their own using traditional vaccines. But Farzan, as well as Johnson, wants to get around the immune system entirely.

Farzan and his colleagues have taken Johnson’s research one step further, engineering a gene that would code for an artificial antibody more powerful than anything that’s ever been seen in humans.
Antibodies do their work by recognizing and latching on to signature molecules coating invading cells. While most BNABs grab on to one key molecular site conserved across all HIV strains in order to disable them, Farzan's artificial antibody grabs on to an additional one essential to the virus's attack.

With the $5.8 million from the Gates Foundation, Farzan will first test the artificial antibody in cells and then in animals to make sure that it's safe. Eventually, the antibody — wrapped in its viral packaging — can be tested as a vaccine in individuals at high risk of contracting HIV to see how well it protects them from infection.

But even if it is successful, Farzan and others caution that a genetically engineered HIV vaccine is still many years and many many millions of dollars away.

"It seems to be extremely powerful — that's why so much of the scientific community has gotten excited," Thomas Hassell, vice president of vaccine development for the International AIDS Vaccine Initiative, told BuzzFeed News.

"But will it prove to be powerful enough in the face of HIV, which is so extraordinary in its diversity, so cunning in its escape mechanisms? You need a truly extraordinary response to be able to deal with that extraordinary of an invader."

http://www.buzzfeed.com/azeenghorayshi/bill-gates-hiv-vaccine

[MitchMiller]

Here's the original article.  It was posted here previously... seems to hold a lot of promise.

In a remarkable new advance against the virus that causes AIDS, scientists from the Jupiter, Florida campus of The Scripps Research Institute (TSRI) have announced the creation of a novel drug candidate that is so potent and universally effective, it might work as part of an unconventional vaccine.

The research, which involved scientists from more than a dozen research institutions, was published February 18 online ahead of print by the journal Nature.

The study shows that the new drug candidate blocks every strain of HIV-1, HIV-2 and SIV (simian immunodeficiency virus) that has been isolated from humans or rhesus macaques, including the hardest-to-stop variants. It also protects against much-higher doses of virus than occur in most human transmission and does so for at least eight months after injection.

"Our compound is the broadest and most potent entry inhibitor described so far," said Michael Farzan, a TSRI professor who led the effort. "Unlike antibodies, which fail to neutralize a large fraction of HIV-1 strains, our protein has been effective against all strains tested, raising the possibility it could offer an effective HIV vaccine alternative."

Blocking a Second Site

When HIV infects a cell, it targets the CD4 lymphocyte, an integral part of the body's immune system. HIV fuses with the cell and inserts its own genetic material -- in this case, single-stranded RNA -- and transforms the host cell into a HIV manufacturing site.

The new study builds on previous discoveries by the Farzan laboratory, which show that a co-receptor called CCR5 contains unusual modifications in its critical HIV-binding region, and that proteins based on this region can be used to prevent infection.

With this knowledge, Farzan and his team developed the new drug candidate so that it binds to two sites on the surface of the virus simultaneously, preventing entry of HIV into the host cell.

"When antibodies try to mimic the receptor, they touch a lot of other parts of the viral envelope that HIV can change with ease," said TSRI Research Associate Matthew Gardner, the first author of the study with Lisa M. Kattenhorn of Harvard Medical School. "We've developed a direct mimic of the receptors without providing many avenues that the virus can use to escape, so we catch every virus thus far."

The team also leveraged preexisting technology in designing a delivery vehicle -- an engineered adeno-associated virus, a small, relatively innocuous virus that causes no disease. Once injected into muscle tissue, like HIV itself, the vehicle turns those cells into "factories" that could produce enough of the new protective protein to last for years, perhaps decades, Farzan said.

Data from the new study showed the drug candidate binds to the envelope of HIV-1 more potently than the best broadly neutralizing antibodies against the virus. Also, when macaque models were inoculated with the drug candidate, they were protected from multiple challenges by SIV.

"This is the culmination of more than a decade's worth of work on the biochemistry of how HIV enters cells," Farzan said. "When we did our original work on CCR5, people thought it was interesting, but no one saw the therapeutic potential. That potential is starting to be realized."

http://www.sciencedaily.com/releases/2015/02/150218073059.htm?utm_source=feedburner&utm_medium=email&utm_campaign=Feed%3A+sciencedaily%2Fhealth_medicine%2Fhiv_and_aids+%28HIV+and+AIDS+News+--+ScienceDaily%29