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Engineering HIV immunity
For rapidly mutating viruses such as HIV, antibodies that can neutralize more than one strain may have real potential as a therapeutic. Now, Williams et al. examine the ontogeny of broadly neutralizing antibodies (bnAbs) to the distal portion of the membrane-proximal external region (MPER) of HIV-1 gp41. They found similar clonal lineages of an MPER bnAb from both memory B cells and plasma, highlighting the viability of plasma as a source of bnAbs. These lineages shared an autoreactive unmutated common ancestor, suggesting that tolerance must be overcome for bnAb induction. The authors then engineered chimeric antibodies from the plasma and memory B cells that neutralized most HIV-1 strains.
Abstract
Induction of broadly neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development. Antibody 10E8, reactive with the distal portion of the membrane-proximal external region (MPER) of HIV-1 gp41, is broadly neutralizing. However, the ontogeny of distal MPER antibodies and the relationship of memory B cell to plasma bnAbs are poorly understood. HIV-1–specific memory B cell flow sorting and proteomic identification of anti-MPER plasma antibodies from an HIV-1–infected individual were used to isolate broadly neutralizing distal MPER bnAbs of the same B cell clonal lineage. Structural analysis demonstrated that antibodies from memory B cells and plasma recognized the envelope gp41 bnAb epitope in a distinct orientation compared with other distal MPER bnAbs. The unmutated common ancestor of this distal MPER bnAb was autoreactive, suggesting lineage immune tolerance control. Construction of chimeric antibodies of memory B cell and plasma antibodies yielded a bnAb that potently neutralized most HIV-1 strains.
- Copyright © 2017, American Association for the Advancement of Science
