The Antibody Project
Devising a vaccine that can elicit effective antibodies against HIV remains one of the greatest challenges of modern science. This is because HIV changes its genetic makeup (mutates) so fast that it continuously evades targeting by the immune response.
Yet researchers have long known that after a few years of infection, a minority of HIV-positive people produce antibodies that can neutralize a broad spectrum of HIV variants. Though this does not typically prevent their infections from progressing, scientists hypothesize that if such broadly neutralizing antibodies could be induced before exposure to HIV—through vaccination—their presence could prevent the virus from establishing infection.
IAVI launched the Neutralizing Antibody Consortium (NAC) in 2002 to study the molecular structure and biochemistry of known broadly neutralizing antibodies and to use this information to design (reverse engineer) potentially powerful AIDS vaccine candidates. But it quickly became clear that more broadly neutralizing antibodies were needed to inform this approach. In response, IAVI and the NAC in 2006 launched a project of unprecedented scale and ambition to hunt for such antibodies around the world. The project, named Protocol G, enlisted partner research centers in seven sub-Saharan African countries as well as in Thailand, Australia, the United Kingdom and the United States. Upward of 1,800 healthy HIV-positive volunteers participated in the effort. Blood samples were sent to the biotechnology company Monogram Biosciences, which worked with IAVI and NAC researchers to screen these samples for broadly neutralizing activity against HIV. Samples that showed the broadest and most potent neutralizing activity against HIV were sent to four different laboratories.
Most went to Theraclone Sciences, a small biotech company that had won a grant from IAVI’s Innovation Fund to adapt its antibody isolation technology to HIV vaccine research. In 2009, this partnership isolated the first new broadly neutralizing antibodies to HIV seen in a decade and the first to have been isolated from donors in developing countries, where the majority of new HIV infections occur.
Since then, IAVI, the NAC, Theraclone and Monogram have collaborated to isolate and characterize 19 new broadly neutralizing antibodies from the Protocol G blood specimens. Further, researchers at the Vaccine Research Center (VRC) of the United States National Institutes of Health (NIH) have independently isolated several such antibodies, including one picked out of a Protocol G sample. The unique molecular structures targeted by some of these antibodies have been described by researchers at the NAC and the VRC. Researchers have elucidated the genetic origins of one family of broadly neutralizing antibodies and traced the molecular paths by which they evolve into potent neutralizers of HIV. A team of scientists led by NAC and IAVI researchers have already engineered a prototype immunogen—the active ingredient of a vaccine—based on insights gleaned from such studies. Laboratory studies suggest this reverse-engineered immunogen could have the potential to kick-start the maturation of a highly potent broadly neutralizing antibody against HIV.
Many of the broadly neutralizing antibodies isolated by IAVI and NAC researchers have also been distributed to dozens of external researchers to assist in their work. All this information is being mined to guide the design and development of a new and perhaps more potent generation of AIDS vaccine candidates.