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TitleKappa chain maturation helps drive rapid development of an infant HIV-1 broadly neutralizing antibody lineage.
Journal, issue, pagesNat Commun, Vol. 10, Issue 1, Page 2190, Year 2019
Publish dateMay 16, 2019
AuthorsCassandra 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 / Frederick A Matsen Iv / Julie Overbaugh /
PubMed AbstractHIV-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 ...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 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.
External linksNat Commun / PubMed:31097697 / PubMed Central
MethodsEM (single particle)
Resolution4.8 Å
Structure data

9166

6mn7

EMDB-9166, PDB-6mn7:
Cryo-EM structure of BG505.SOSIP.664 in complex with BF520.1 antigen binding fragment
Method: EM (single particle) / Resolution: 4.8 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • human immunodeficiency virus 1
  • homo sapiens (human)
KeywordsVIRAL PROTEIN / Complex / Broadly neutralizing antibody

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