RT Journal Article
SR Electronic
T1 Rapid development of an infant-derived HIV-1 broadly neutralizing antibody lineage
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 416032
DO 10.1101/416032
A1 Cassandra A Simonich
A1 Laura Doepker
A1 Duncan Ralph
A1 James A Williams
A1 Amrit Dhar
A1 Zak Yaffe
A1 Lauren Gentles
A1 Christopher T Small
A1 Brian Oliver
A1 Vladimir Vigdorovich
A1 Vidya Mangala Prasad
A1 Ruth Nduati
A1 D Noah Sather
A1 Kelly K Lee
A1 A Matsen Frederick IV
A1 Julie Overbaugh
YR 2018
UL http://biorxiv.org/content/early/2018/09/13/416032.abstract
AB 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. We developed computational methods to reconstruct the developmental lineage of BF520.1, the first example of a HIV-specific broadly neutralizing antibody (bnAb) from an infant. The BF520.1 inferred naïve precursor binds HIV Env and a bnAb evolved within six months of infection and required only 3% mutation. Mutagenesis and structural analyses revealed that for this infant bnAb, substitutions in the kappa chain were critical for activity, particularly in CDRL1. Overall, the developmental pathway of this infant antibody includes features distinct from adult antibodies, including several that may be amenable to better vaccine responses.