Kappa chain maturation helps drive rapid development of an infant HIV-1 broadly neutralizing antibody lineage
Year: 2019
Type: article
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 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.
Source: Nature Communications
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,200
Funders: National Science Foundation, Howard Hughes Medical Institute, Simons Foundation, Arnold and Mabel Beckman Foundation, Washington Research Foundation, University of Washington, National Institutes of Health, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases
Awards: Characterizing broadly neutralizing antibody responses of HIV-1-infected infants, G3895467255, G454452693, University of Washington Medical Scientist Training Program, IGERT-CIF21: Big Data U: A Program for Integrated Multidisciplinary Education and Research for Big Data Science, Leveraging deep sequencing data to understand antibody maturation, Dynamics and Evolution of Immune Responses to Influenza Viruses, G9000142776, STD and AIDS Research Training Grant, University of Washington/Fred Hutch Center for AIDS Research
OpenAlex ID: W2945941055