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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.”