@article{060409c0700648bea988f654e1baa50a,
title = "A generalized HIV vaccine design strategy for priming of broadly neutralizing antibody responses",
abstract = "Vaccine induction of broadly neutralizing antibodies (bnAbs) to HIV remains a major challenge. Germline-targeting immunogens hold promise for initiating the induction of certain bnAb classes; yet for most bnAbs, a strong dependence on antibody heavy chain complementarity-determining region 3 (HCDR3) is a major barrier. Exploiting ultradeep human antibody sequencing data, we identified a diverse set of potential antibody precursors for a bnAb with dominant HCDR3 contacts. We then developed HIV envelope trimer–based immunogens that primed responses from rare bnAb-precursor B cells in a mouse model and bound a range of potential bnAb-precursor human na{\"i}ve B cells in ex vivo screens. Our repertoire-guided germline-targeting approach provides a framework for priming the induction of many HIV bnAbs and could be applied to most HCDR3-dominant antibodies from other pathogens.",
author = "Steichen, {Jon M.} and Lin, {Ying Cing} and Colin Havenar-Daughton and Simone Pecetta and Gabriel Ozorowski and Willis, {Jordan R.} and Laura Toy and Devin Sok and Alessia Liguori and Sven Kratochvil and Torres, {Jonathan L.} and Oleksandr Kalyuzhniy and Eleonora Melzi and Kulp, {Daniel W.} and Sebastian Raemisch and Xiaozhen Hu and Bernard, {Steffen M.} and Erik Georgeson and Nicole Phelps and Yumiko Adachi and Michael Kubitz and Elise Landais and Jeffrey Umotoy and Amanda Robinson and Bryan Briney and Wilson, {Ian A.} and Burton, {Dennis R.} and Ward, {Andrew B.} and Shane Crotty and Batista, {Facundo D.} and Schief, {William R.}",
note = "Funding Information: We thank H. Gristick and P. Bjorkman for providing atomic coordinates of unliganded BG18 Fab in advance of publication (17) and C. Corbaci for graphical design assistance for the summary. Funding: This work was supported by the National Institute of Allergy and Infectious Diseases (NIAID) UM1 Al100663 (Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery) and UM1 AI144462 (Scripps Consortium for HIV/AIDS Vaccine Development) (to W.R.S., F.D.B., S.C., A.B.W., and D.R.B) and NIAID R01 AI113867 (to W.R.S.); by the Ragon Institute of MGH, MIT, and Harvard (to F.D.B., W.R.S., and D.R.B.); by the International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Consortium (NAC) and Center (to W.R.S., A.B.W., I.A.W., and D.R.B.); and through the Collaboration for AIDS Vaccine Discovery funding for the IAVI NAC Center (to W.R.S., A.B.W., I.A.W., and D.R.B.). Publisher Copyright: {\textcopyright} 2019 American Association for the Advancement of Science. All rights reserved.",
year = "2019",
month = dec,
day = "6",
doi = "https://doi.org/10.1126/science.aax4380",
language = "English",
volume = "366",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6470",
}