New Antibodies for HIV: Fresh Hope for a Vaccine?

[Guest guest]

New Antibodies for HIV: Fresh Hope for a Vaccine?

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.

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.

" 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. 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. "

Dr Diwakar Tejaswi

MBBS(Gold Medalist); MCH; FCCP; Ph.D

Consultant Physician and Medical Director

Public Awareness for Healthful Approach for Living (PAHAL)

Harinarayan Complex, Exhibition Road, Patna 800001, India

Telefax: +91-612-2206964; Mobile: +91-9835078298/ 9431829397;

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