[health-vn] New Antibodies for HIV: Fresh Hope for a Vaccine?

[Vern Weitzel]

http://www.time.com/time/health/article/0,8599,1920332,00.html

Thursday, Sep. 03, 2009
New Antibodies for HIV: Fresh Hope for a Vaccine?
By Alice Park

Scientists probably know more about HIV than any other pathogen, but despite 
that fact, they have had frustratingly little success in applying their 
knowledge toward a vaccine against the virus.

Now, after more than 15 years of trial and error in the field, researchers at 
the Scripps Research Institute and the International AIDS Vaccine Initiative 
(IAVI) report they have discovered two powerful new antibodies to HIV, which may 
potentially lead to the development of a way to immunize against the virus. (See 
TIME's photo essay "Access to Life.")

While the new antibodies are not the first of the so-called broadly neutralizing 
antibodies that have been isolated from HIV-positive patients, they appear, at 
least in the lab, to be 10 times more effective at disarming the virus than 
earlier versions. They are also effective against a broad array of HIV strains 
that span nearly every continent, from Europe and North America to Asia and 
Africa. That would make them ideal candidates for a new vaccine — one that could 
actually protect people from becoming infected with HIV at all.

In a way, it's a back-to-the-future approach. Vaccines, including many of the 
familiar ones that target childhood diseases such as measles and mumps, work by 
training the immune system to generate antibodies against a foreign bacteria or 
virus. Made by immune cells known as B lymphocytes, these antibodies bind to 
specific portions of a virus and then hamper that virus from infecting healthy 
cells. Eventually, the piggybacked antibody also tags the invading virus for 
destruction by other immune cells, known as T cells. (See TIME's AIDS covers.)

"We looked at 162 different [HIV] viruses, and these antibodies neutralized 120 
to 130 of strains from all across the world," says Dennis Burton of Scripps, the 
lead author of the study, published in the Sept. 4 issue of Science. "They 
certainly don't get everything. But if you are able to get 80% or more of 
viruses circulating out there with one single antibody, that's terrific. That's 
really, really good, considering how variable these viruses are."

That variability has been the biggest challenge for HIV vaccinemakers. HIV 
mutates so rapidly once it finds a new home in an infected patient that it's 
hard for researchers to keep pace and target the portions of the virus that are 
conserved. It was a lesson that Merck learned the hard way in 2007, when trials 
of its promising AIDS-vaccine candidate not only failed to protect people from 
acquiring HIV but in fact appeared to raise the risk of infection in inoculated 
people, compared with those who did not get the vaccine. (It's not clear why 
Merck's compound failed so miserably, but researchers believe it may have to do 
with the vector, an inactivated cold virus, that was used to ferry the 
immunity-triggering HIV proteins into the body; some people may have developed 
enough natural tolerance to the common-cold virus that their immune system did 
not react to it, or to the viral payload piggybacked on it, at all.)

Given that recent setback, Burton's team decided on a different approach. 
Instead of trying to identify which portions of HIV elicited the best immune 
response — a strategy that has been attempted without much success in not just 
Merck's but other previous vaccine efforts as well — they started with a pool of 
antibodies they knew could neutralize HIV and then backtracked to determine how 
to entice the immune system into producing them. To find the most effective 
antibodies, Burton's team used the latest biological and computational screening 
techniques, which emerged from genome-sequencing technologies. They collected 
blood serum from 1,800 HIV-infected people from around the world, then screened 
these virus-laden samples against B cells to see how many of the HIV strains the 
immune cells would recognize. To their surprise, the B cells were able to 
neutralize a fair number of the viruses, but two of the antibodies produced by 
the cells clearly stood out as more potent than the rest.

"This paper is important because what the authors were able to do is identify 
many more neutralizing antibodies than what we find in the serum of patients," 
says Dr. Anthony Fauci, director of the National Institute on Allergy and 
Infectious Disease, which raises the question, "Why don't people make antibodies 
to all of these HIV strains? Why isn't their blood naturally loaded with these 
antibodies?"

One reason may be that HIV is able to hide from B cells, jealously guarding its 
most conserved, and therefore most vulnerable, portions from view. That would 
prevent the body from creating the right neutralizing antibodies against the 
virus. But the two new antibodies reported in Science target a less hidden 
region of the viral coat, so it may be possible that if a new vaccine is 
developed, it could stimulate the immune system to marshal a robust enough force 
of antibodies to stop HIV.

The new discoveries have renewed some AIDS researchers' faith in the vaccine 
approach. In the lab, says Fauci, scientists know that these antibodies can 
effectively stop HIV in its tracks, starving it out by preventing it from 
binding to immune cells that provide it with the nutrients and machinery it 
needs to grow and reproduce.

The next and perhaps greater challenge is making the right concoction of viral 
proteins that will stimulate the immune system to churn out these antibodies in 
large amounts. "Now that we have the antibodies, we have to go back and create 
the [immune signal] that produces these antibodies," says Seth Berkley, 
president and CEO of IAVI. After that, the task is to package that immune signal 
in the form of a usable vaccine. Says Fauci: "And that's a big catch, a second 
hurdle that we have not gone over yet."