C-106 Pan-neutralizing antibodies derived from human plasma targeting a new epitope

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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.

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