@article{80f1ea7d9910499b9a73683cf961361c,
title = "Sequencing HIV-neutralizing antibody exons and introns reveals detailed aspects of lineage maturation",
abstract = "The developmental pathways of broadly neutralizing antibodies (bNAbs) against HIV are of great importance for the design of immunogens that can elicit protective responses. Here we show the maturation features of the HIV-neutralizing anti-V1V2 VRC26 lineage by simultaneously sequencing the exon together with the downstream intron of VRC26 members. Using the mutational landscapes of both segments and the selection-free nature of the intron region, we identify multiple events of amino acid mutational convergence in the complementarity-determining region 3 (CDR3) of VRC26 members, and determine potential intermediates with diverse CDR3s to a late stage bNAb from 2 years prior to its isolation. Moreover, we functionally characterize the earliest neutralizing intermediates with critical CDR3 mutations, with some emerging only 14 weeks after initial lineage detection and containing only ~6% V gene mutations. Our results thus underscore the utility of analyzing exons and introns simultaneously for studying antibody maturation and repertoire selection.",
author = "Johnson, {Erik L.} and Doria-Rose, {Nicole A.} and Jason Gorman and Bhiman, {Jinal N.} and Schramm, {Chaim A.} and Vu, {Ashley Q.} and Law, {William H.} and Baoshan Zhang and Valerie Bekker and {Abdool Karim}, {Salim S.} and Ippolito, {Gregory C.} and Lynn Morris and Moore, {Penny L.} and Kwong, {Peter D.} and Mascola, {John R.} and George Georgiou",
note = "Funding Information: We are grateful to the participants of the CAPRISA 002 study. CAPRISA is funded by the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), and the U.S. Department of Health and Human Services (grant: AI51794). This work was supported by Leidos Biomedical Research Inc. contract 15 × 219 (G.G.), Defense Threat Reduction Agency (DTRA) contract HDTRA1–12-C-0105 (G.G.) and NIH grant 1 R56AI106006 (G.G.). This work was also supported by NIH U01 grant AI116086–01 (P.L.M., L.M.) and in part, by the intramural research program of the Vaccine Research Center, NIAID, NIH (J.R.M., P.D.K). P.L.M. is supported by the South African Research Chairs Initiative of the DST and NRF of South Africa (98341). We would like to thank the University of Texas at Austin Genome Sequencing and Analysis Facility for performing high-throughput sequencing. Publisher Copyright: {\textcopyright} 2018, The Author(s).",
year = "2018",
month = dec,
day = "1",
doi = "10.1038/s41467-018-06424-6",
language = "English (US)",
volume = "9",
journal = "Nat Commun",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}