Sanofi, NIH Researchers Develop "Three-In-One" Antibodies as Potential Intervention for HIV/AIDS

In a study published in the journal Science, researchers produced genetically engineered antibodies with the highest activity and breadth of coverage yet seen against human immunodeficiency virus (HIV-1).

Natural antibodies recognize a single target on a foreign protein. In this study, antibodies were engineered to recognize three different target sites in one molecule. These HIV "trispecific" antibodies were highly effective in suppressing virus growth and infection. 

"Unlike natural antibodies, trispecific antibodies engage multiple targets in a single product. This approach to multi-targeting provides an opportunity to improve protection against HIV and represents a foundation for potential new treatments of cancer, immune, and infectious diseases," said Gary Nabel, Chief Scientific Officer and Senior Vice President of Sanofi, and lead co-author of the paper in Science.

A key challenge in using broadly neutralizing HIV antibodies to tackle the ongoing HIV pandemic is overcoming the remarkable genetic diversity of viruses around the world.

The trispecific antibodies showed better coverage than any previously-studied antibody, neutralizing 99% of more than 200 diverse strains of HIV-1. One of the trispecific antibodies that recognized the CD4 binding site, the membrane proximal external region (MPER), and the V1V2 glycan site of HIV fully protected monkeys against infection from a mixture of two simian/human immunodeficiency viruses (SHIV). These viruses had shown resistance to single-target antibodies.

The trispecific antibody builds on proprietary technology developed by Sanofi, and was identified after dozens of different bispecific and trispecific combinations were tested. Sanofi is now manufacturing this trispecific antibody for use in a Phase I clinical trial expected to begin in 2018 at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

Today's published results come from the work of Sanofi, NIAID, Harvard Medical School, The Scripps Research Institute, and the Ragon Institute of MGH, MIT and Harvard.

The trispecific antibodies are currently in preclinical development, and their safety and efficacy have not been fully evaluated by any regulatory authority.