National Academy of Sciences, Proceedings of the National Academy of Sciences, 16(113), p. 4446-4451, 2016
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Significance When HIV neutralizing antibody (Ab) responses occur, they are often mediated by Abs with exceptional levels of somatic mutation. An exception are HIV neutralizing Abs that feature long heavy-chain complementarity-determining region 3 (HCDR3) regions, such as the Ab PG9. Relative to many other HIV broadly neutralizing Abs (bnAbs), PG9 has fewer somatic mutations than most potent bnAbs. Here we used deep-sequencing and computational methods to identify a panel of HCDR3 sequences in HIV-naïve donors that mediated binding and neutralization of HIV by mimicking the bnAb PG9 long HCDR3 region when expressed in the context of the rest of the PG9 antibody sequence. Thus, it may be possible for structure-based vaccine design efforts to engage long HCDR3s available in the HIV-naïve Ab repertoire and elicit a neutralizing response.