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Rapid development of an infant-derived HIV-1 broadly neutralizing antibody lineage

By Cassandra A Simonich, Laura Doepker, Duncan Ralph, James A Williams, Amrit Dhar, Zak Yaffe, Lauren Gentles, Christopher T Small, Brian Oliver, Vladimir Vigdorovich, Vidya Mangala Prasad, Ruth Nduati, D. Noah Sather, Kelly K. Lee, A Matsen Frederick, Julie Overbaugh

Posted 13 Sep 2018
bioRxiv DOI: 10.1101/416032 (published DOI: 10.1038/s41467-019-09481-7)

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.

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