New Antibodies Found that Cripple HIV

New Antibodies Found that Cripple HIV

IAVI and affiliated researchers have discovered two powerful new antibodies to HIV that reveal what may be an Achilles heel on the virus. The findings are the result of a worldwide effort launched by IAVI in 2006 to find new antibodies that neutralize a wide variety of strains of HIV circulating in the world. The study was published in the journal Science.

HIV, the virus that causes AIDS, is the most mutable pathogen ever encountered by modern science. It changes at a furious rate, which helps it evade the body’s immune system. Today, countless variations of the virus infect people around the world. To be effective an AIDS vaccine would have to work against many versions of HIV.

The two new broadly neutralizing antibodies are the first to be discovered in more than a decade, and the first to be isolated from donors in developing countries where the pandemic is raging. Now researchers will try to exploit the newfound vulnerability on the virus to craft new approaches to designing an AIDS vaccine.

“The findings are an exciting advance because now we’ve got a new, potentially better target on HIV to focus our efforts for vaccine design,” said Wayne Koff, senior vice president of research and development at IAVI. “And having identified this one, we’re set up to find more.”



What are broadly neutralizing antibodies?

Antibodies are infection-fighting protein molecules that tag, neutralize and help destroy toxins and invading pathogens. They are secreted by immune cells known as B lymphocytes (a kind of white blood cell) in response to stimulation by antigens, which are molecules found on the invading pathogen. Each antibody binds only to the specific antigen that stimulated its production. HIV attacks and quickly overwhelms the body’s immune system, but a minority of people naturally produce broadly neutralizing antibodies—ones that target multiple strains of HIV and prevent the virus from infecting cells. Isolating these antibodies gives vaccine researchers valuable insight into fighting the virus.



Why is this discovery important?

Before this discovery, researchers had found just four antibodies widely considered to be broadly neutralizing, and those four were associated with a strain of the virus circulating primarily in the Americas, Europe and Australia. The new antibodies came from a donor in the developing world, where 95% of new infections occur.

They also reveal a new vulnerable spot on HIV, binding to a potentially easier-to-reach patch on the virus that no previously known antibodies targeted. This is extremely important—it provides a new target for vaccine designers to exploit. And the antibodies appear to be highly potent as well, which means they bind to the virus tightly. This is important because—if they can be elicited by vaccination—the body might not have to produce large amounts of the antibodies to gain protection from HIV.



What’s the next step?

The new antibodies will now be closely studied by researchers in IAVI’s Neutralizing Antibody Consortium, who will work out the molecular structure and the precise mechanism by which the antibodies bind to HIV. With this information in hand, they will begin working to design novel immunogens—the active ingredient in vaccines—to elicit these antibodies in all people. If they succeed, the immunogens will be put through the preclinical process to produce an industrially viable vaccine candidate for further development.



How were the antibodies found?

The discovery of the new antibodies is the result of a global collaboration among IAVI, the Scripps Research Institute, private biotech firms and more than a dozen clinical research centers around the world.

The Antibody Project

The Antibody Project began with an IAVI-sponsored clinical study called Protocol G, a global hunt for new broadly neutralizing antibodies against HIV. The effort involved scientists from North America, Europe, Africa and Asia. The study was unprecedented in scope and ambition. Here’s how it worked:

Blood samples were collected from more than 1,800 HIV-positive people across the world. This effort capitalized on the IAVI-supported network of clinical research centers in sub-Saharan Africa. Other researchers also took part. The samples were collected and processed at IAVI’s Human Immunology Laboratory in London.

Next, the samples needed to be tested for neutralizing activity against HIV. IAVI scientists had a hunch that traditional screening methods weren’t picking up the presence of every powerful antibody. They were right. IAVI researchers worked with a private biotech firm, Monogram Biosciences, and an independent biostatistician to create a new process that more accurately predicted whether a given sample contained broadly neutralizing antibodies. Researchers scored the samples in terms of how many types of HIV they neutralized, and separated the top 10% for further study.

These most promising samples then went to four IAVI research partners—HuMabs, in Bellinzona, Switzerland; Rockefeller University, in New York City; the IAVI Neutralizing Antibody Center at The Scripps Research Institute, in La Jolla, California; and Theraclone Sciences, in Seattle, Washington. Each would employ a different technology in an effort to pluck out new antibodies.

The Theraclone team was the first to succeed, finding the two powerful new antibodies against HIV.

Isolating antibodies can be painstaking work. But Theraclone, a company that had been working outside the HIV field, had a unique process that it adapted to HIV work with financing from IAVI’s Innovation Fund, which is co-funded by the Bill & Melinda Gates Foundation. The team used a system designed to expose the entire array of antibodies from a blood sample. Antibodies with broadly neutralizing potential were identified and traced to their corresponding antibody-forming cells. Using recombinant DNA technology, broadly neutralizing antibody genes were isolated from these cells to enable the production of unlimited quantities of the antibody clones for research.

With a large pool of HIV-positive donors from Protocol G now identified whose serum contains broadly neutralizing antibodies to HIV, this global collaboration is likely to generate findings that will benefit the vital enterprise of accelerating AIDS vaccine research and development.

“The story of the discovery of these two new antibodies demonstrates the power of the collaboration that formed to produce this advance. This is what can happen when you have researchers from the global North and South, from academia and industry, from within and outside the HIV field, working together in a framework to speed innovation,” said Seth Berkley, president and CEO of IAVI. “By working in this manner, I am confident we will continue to move toward solving the AIDS vaccine challenge, one of the greatest scientific and public health challenges of our time.”