Using a new methodology to obtain the sequences of antibodies in circulation, we have discovered a family of antibodies of remarkable breadth and potency: the N49 P series. Some members of this family have the capability to neutralize 100% of isolates tested in a Tier 1-3 multiclade 117 pseudovirus panel, including all pseudovirsuses that were resistant to other mAbs tested in the same panel (PGT121, GT 128, PGT 145, PGDM1400, PGT 151, 10-107 4, 10E8, PG9, PG16, 3BNC117, NIH 45-46, 8ANC195, VRC01, and VRC07). Elisa studies and sequence analysis show the N49 mAbs to have some characteristics of CD4-binding site antibodies. However, crystallographic studies show a bypassing of the CD4-binding site pocket in favor on the inner domain. The N49 P series has potential to be useful in passive immunization and prophylactic vaccine design for HIV-1.
*Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201
†Department of Medicine, Baltimore VA Medical Center, Baltimore, MD 21201
‡Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, 3 Blackfan Circle, Boston, MA 02115
§Atreca, Inc., Redwood City, CA 94063