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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 in 2009. In 2011, a team of researchers at and associated with the IAVI, The Scripps Research Institute, Theraclone and Monogram Biosciences Inc., a LabCorp company, reported the isolation of 17 additional new antibodies capable of neutralizing a broad spectrum of variants of 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.