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Background VRC01 and related antibodies target the CD4 binding site (CD4bs), are broadly neutralizing and highly potent, and have undergone high levels of somatic hypermutation. To optimize such antibodies for passive immunization and to further understand antibody development, we reverted three CD4bs antibodies towards their putative germlines and analyzed the effects on breadth and potency. Interestingly, we also identified key germline reversion mutations that increased neutralization potential.

Partial germline reversions can increase VRC07 potency and breadth