Kappa chain maturation helps drive rapid development of an infant HIV-1 broadly neutralizing antibody lineage.

ABSTRACT: HIV-infected infants develop broadly neutralizing plasma responses with more rapid kinetics than adults, suggesting the ontogeny of infant responses could better inform a path to achievable vaccine targets. Here we reconstruct the developmental lineage of BF520.1, an infant-derived HIV-specific broadly neutralizing antibody (bnAb), using computational methods developed specifically for this purpose. We find that the BF520.1 inferred naive precursor binds HIV Env. We also show that heterologous cross-clade neutralizing activity evolved in the infant within six months of infection and that, ultimately, only 2% SHM is needed to achieve the full breadth of the mature antibody. Mutagenesis and structural analyses reveal that, for this infant bnAb, substitutions in the kappa chain were critical

SUBMITTER: Simonich CA 

PROVIDER: S-EPMC6522554 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature