An antibody that targets and neutralizes HIV’s CD4 binding site across a broad range of viral strains could be a new treatment option for the disease, according to two papers published online May 20 in Science.
In a phase I trial, researchers saw an enhanced antibody response over 6 months in 15 viremic HIV-1 infected individuals given a single injection of the broadly neutralizing antibody 3BNC117, compared with untreated controls, suggesting the immunotherapy may enhance the immune response against HIV-1.
“The absolute change in neutralizing activity varied between viruses and individuals, ranging from small effects to dramatic increases,” wrote Dr. Till Schoofs, from the Laboratory of Molecular Immunology at Rockefeller University, New York, and coauthors.
The antibody was also given to 12 individuals on antiretroviral therapy, with no detectable or very low viremia, with the result being a significantly less pronounced increase in neutralizing activity, compared with that seen in the non–ART treated individuals (Science. 2016 May 20. doi: 10.1126/science.aaf0972).
In a second paper, the same group of researchers analyzed the abundance of the antibody and viral load decline in the treated individuals and attempted to explain why their study observations did not fit with predictions.
Their modeling suggested that not only was the antibody binding to free virus particles but was also clearing HIV-1 infected cells.
They confirmed this with a study in HIV-1 infected mice, which showed treatment with the antibody was associated with accelerated clearance of HIV-infected cells, and in cells infected with patient isolates where the antibody achieved accelerated clearance of HIV-infected CD4+ T cells (Science. 2016 May 20. doi: 10.1126/science.aaf1279).
“Our mathematical analysis of patient data, and the antibody-mediated reduction in infected cells seen in adoptive transfer experiments establish that bNAbs [broadly neutralizing antibodies] alter the half-life of infected cells,” wrote Ching-Lan Lu, from the Laboratory of Molecular Immunology at Rockefeller University, New York, and coauthors.
“The finding that antibodies can clear infected cells in vivo has significant implications for therapies aimed at HIV prevention and viral reservoir reduction or elimination.”
The first study was supported by the Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery, the Robertson Foundation, NIH Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, the University of Pennsylvania Center for AIDS Research, the National Institutes of Health, and HIVRAD.
The second study was supported by Collaboration for AIDS Vaccine Discovery, the National Center for Advancing Translational Sciences; NIH Clinical and Translational Science Award, the NIH Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, the Bill and Melinda Gates Foundation, the Robertson Foundation, the German Research Foundation, the American Foundation for AIDS research, the Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, Harvard, and the National Institute of Allergy and Infectious Diseases.
One author from both studies is an inventor on a pending patent for 3BNC117 by Rockefeller University, New York.