Abstract
Understanding the molecular basis of HIV Env-specific broadly neutralizing antibodies (bnAbs) development especially, at early stages, is key for germline-targeting vaccine design strategies. Umotoy et al. mapped the development of a VRC01-class bnAb lineage that achieved breadth in 2 years, revealing early binding to the N276-glycan during affinity maturation, which may have implications for vaccine design.
| Original language | English |
|---|---|
| Pages (from-to) | 141-154.e6 |
| Journal | Immunity |
| Volume | 51 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 16 Jul 2019 |
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In: Immunity, Vol. 51, No. 1, 16.07.2019, p. 141-154.e6.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Rapid and Focused Maturation of a VRC01-Class HIV Broadly Neutralizing Antibody Lineage Involves Both Binding and Accommodation of the N276-Glycan
AU - The IAVI Protocol C Investigators
AU - The IAVI African HIV Research Network
AU - Umotoy, Jeffrey
AU - Bagaya, Bernard S.
AU - Joyce, Collin
AU - Schiffner, Torben
AU - Menis, Sergey
AU - Saye-Francisco, Karen L.
AU - Biddle, Trevor
AU - Mohan, Sanjay
AU - Vollbrecht, Thomas
AU - Kalyuzhniy, Oleksander
AU - Madzorera, Sharon
AU - Kitchin, Dale
AU - Lambson, Bronwen
AU - Nonyane, Molati
AU - Kilembe, William
AU - Poignard, Pascal
AU - Schief, William R.
AU - Burton, Dennis R.
AU - Murrell, Ben
AU - Moore, Penny L.
AU - Briney, Bryan
AU - Sok, Devin
AU - Landais, Elise
N1 - Funding Information: IAVI’s work is made possible by generous support from many donors including: the Bill & Melinda Gates Foundation, the Ministry of Foreign Affairs of Denmark, Irish Aid, the Ministry of Finance of Japan in partnership with The World Bank, the Ministry of Foreign Affairs of the Netherlands, the Norwegian Agency for Development Cooperation (NORAD), the United Kingdom Department for International Development (DFID), and the United States Agency for International Development (USAID). The full list of IAVI donors is available at www.iavi.org . This study was made possible by the generous support of the American people through USAID. The contents are the responsibility of the International AIDS Vaccine Initiative and do not necessarily reflect the views of USAID or the United States Government. This work was also supported by National Institute of Health (NIH) Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery Grant UM1AI100663 to BB, DS and DRB, as well as the International AIDS Vaccine Initiative Neutralizing Antibody Consortium through the Collaboration for AIDS Vaccine Discovery grants OPP1084519 and OPP1115782. BM was supported by grants R00AI120851 and UM1AI068618 from the National Institute of Allergy and Infectious Diseases (NIAID). The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH. P.L.M. is supported by the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation of South Africa (Grant No 98341). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases, the National Institute of General Medical Sciences or the National Institutes of Health. Funding Information: IAVI's work is made possible by generous support from many donors including: the Bill & Melinda Gates Foundation, the Ministry of Foreign Affairs of Denmark, Irish Aid, the Ministry of Finance of Japan in partnership with The World Bank, the Ministry of Foreign Affairs of the Netherlands, the Norwegian Agency for Development Cooperation (NORAD), the United Kingdom Department for International Development (DFID), and the United States Agency for International Development (USAID). The full list of IAVI donors is available at www.iavi.org. This study was made possible by the generous support of the American people through USAID. The contents are the responsibility of the International AIDS Vaccine Initiative and do not necessarily reflect the views of USAID or the United States Government. This work was also supported by National Institute of Health (NIH) Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery Grant UM1AI100663 to BB, DS and DRB, as well as the International AIDS Vaccine Initiative Neutralizing Antibody Consortium through the Collaboration for AIDS Vaccine Discovery grants OPP1084519 and OPP1115782. BM was supported by grants R00AI120851 and UM1AI068618 from the National Institute of Allergy and Infectious Diseases (NIAID). The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH. P.L.M. is supported by the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation of South Africa (Grant No 98341). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases, the National Institute of General Medical Sciences or the National Institutes of Health. PacBio SMRT sequencing was performed with the support of the Translational Virology Core at the UC San Diego Center for AIDS Research (P30 AI036214), and the IGM Genomics Center, University of California, San Diego, La Jolla, California. We are very grateful to and thank all of the Protocol C participants and clinical investigators, as well as all of the Protocol C project team members for all of the support provided for this study, particularly Matt Price (IAVI and University of California San Francisco, USA), Brendan McAtarsney (London Imperial College, UK) and Jonathan Hare (IAVI and London Imperial College, UK) for clinical data management and coordinating the samples transfers and shipments for this study. Finally we would like to express our gratitude to Christina Corbaci (The Scripps Research Institute, CA, USA) for her expert assistance in the design of the graphical abstract. Conceptualization: S. Menis, W.K. I.P.C.I. & I.A.H.R.N. P.P. B.M. P.L.M. B. Briney, D.S. and E.L. Methodology: S. Menis, B.M. P.L.M. and E.L. Software: C.J. S. Menis, B.M. and B. Briney. Validation: E.L. Formal Analysis: J.U. B. Bagaya, C.J. T.S. B.M. P.L.M. B. Briney, and E.L. Investigation: J.U. B. Bagaya, C.J. T.S. K.F.-S. T.B. S. Mohan, T.V. O.K. S. Madzorera, D.K. B.L. M.N. and E.L. Resources: W.K. I.P.C.I. & I.A.H.R.N. W.R.S. D.R.B. and E.L. Data Curation: B.M. B. Briney, and E.L. Writing ? Original Draft: J.U. B. Briney, and E.L. Writing ? Review & Editing: J.U. B. Bagaya, W.R.S. D.R.B. B.M. P.L.M. B. Briney, D.S. and E.L. Visualization: J.U. T.S. S. Menis, B.M. B. Briney, D.S. and E.L. Supervision: T.S. B.M. P.L.M. B. Briney, D.S. and E.L. Project Administration: E.L. Funding Acquisition: W.R.S. D.R.B. B.M. P.L.M. B. Briney, D.S. and E.L. Some authors have filed a patent application whose subject matter relates to this work. Publisher Copyright: © 2019 The Authors
PY - 2019/7/16
Y1 - 2019/7/16
N2 - Understanding the molecular basis of HIV Env-specific broadly neutralizing antibodies (bnAbs) development especially, at early stages, is key for germline-targeting vaccine design strategies. Umotoy et al. mapped the development of a VRC01-class bnAb lineage that achieved breadth in 2 years, revealing early binding to the N276-glycan during affinity maturation, which may have implications for vaccine design.
AB - Understanding the molecular basis of HIV Env-specific broadly neutralizing antibodies (bnAbs) development especially, at early stages, is key for germline-targeting vaccine design strategies. Umotoy et al. mapped the development of a VRC01-class bnAb lineage that achieved breadth in 2 years, revealing early binding to the N276-glycan during affinity maturation, which may have implications for vaccine design.
UR - http://www.scopus.com/inward/record.url?scp=85068053808&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.immuni.2019.06.004
DO - https://doi.org/10.1016/j.immuni.2019.06.004
M3 - Article
C2 - 31315032
SN - 1074-7613
VL - 51
SP - 141-154.e6
JO - Immunity
JF - Immunity
IS - 1
ER -