“HIV is totally different from other viruses,” Barton Haynes, global health professor and director of the Duke Human Vaccine Institute (DHVI), explained. “It’s one of the fastest-changing life forms on Earth, and it inserts itself into genetic material and hides from the immune system and from drugs. That’s why it’s been so challenging to develop a vaccine and a cure.”
But he and colleagues from Duke and a number of collaborating institutions recently created an extraordinarily potent antibody that can neutralize 99.5% of the HIV strains tested—a significant advance in the fight against the disease. LaTonya Williams, a post-doctoral associate at DHVI, led the study, and Haynes is the senior author. DGHI affiliate Georgia Tomaras also contributed to the study, which was published in Science Immunology.
Haynes said the study yielded three particularly notable results:
After isolating antibodies from an individual who had produced an unusually broad neutralizing antibody, the researchers were able to identify the antibodies’ origin and pathway of development. This new knowledge opens the potential for researchers to design a series of immunogens to recreate these events and use these antibodies to prevent or treat HIV.
The researchers probed that same individual’s plasma and extracted antibodies. Haynes’ colleague George Giorgiou, from the University of Texas at Austin, identified which antibodies belong to the same family of antibodies that they isolated from that individual’s memory B cells. This process, which had never been undertaken before, resulted in the discovery that they all were derived from the same cell, were able to neutralize a broad range of viruses and were similarly potent.
The researchers mixed and matched parts of the plasma antibodies and the memory B cell antibodies until they developed an artificially combined antibody—called the “K3 antibody”—that was broader and more potent than any of the natural antibodies. This antibody, which neutralized 305 out of 308 global isolates, is now a candidate for use in treatment.
One of the researchers’ findings was especially relevant in the global health context. “We found that this antibody was able to neutralize all 100 out of 100 clade C viruses tested,” Williams said. “And that’s important because we know that HIV is very prevalent in Africa, and the predominant clade of viruses in Africa are clade C.”
Given the notoriously diverse range of HIV viruses, the broad neutralization capacity of these antibodies is groundbreaking. And in addition, the researchers believe the antibodies they isolated may lend themselves particularly well to large-scale manufacturing, making them better candidates than other antibodies for future use in a clinical setting.
According to Haynes, the next steps in the research process are to modify the new powerful antibody to further increase its potency and stability, and then determine how to scale up its production.
This work was funded by the National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS grant for the Duke Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery; the Bill and Melinda Gates Foundation; the Interdisciplinary Research Training Program in AIDS; the Duke Center for AIDS Research; the Defense Threat Reduction Agency; and the Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases.