Sequence and Structural Convergence of Broad and Potent HIV Antibodies That Mimic CD4 Binding

Johannes F. Scheid; Hugo Mouquet; Beatrix Ueberheide; Ron Diskin; Florian Klein; Thiago Y.K. Oliveira; John Pietzsch; David Fenyo; Alexander Abadir; Klara Velinzon; Arlene Hurley; Sunnie Myung; Farid Boulad; Pascal Poignard; Dennis R. Burton; Florencia Pereyra; David D. Ho; Bruce D. Walker; Michael S. Seaman; Pamela J. Bjorkman; Brian T. Chait; Michel C. Nussenzweig

doi:10.1126/science.1207227

Sequence and Structural Convergence of Broad and Potent HIV Antibodies That Mimic CD4 Binding

Johannes F. Scheid, Hugo Mouquet, Beatrix Ueberheide, Ron Diskin, Florian Klein, Thiago Y.K. Oliveira, John Pietzsch, David Fenyo, Alexander Abadir, Klara Velinzon, Arlene Hurley, Sunnie Myung, Farid Boulad, Pascal Poignard, Dennis R. Burton, Florencia Pereyra, David D. Ho, Bruce D. Walker, Michael S. Seaman, Pamela J. BjorkmanBrian T. Chait, Michel C. Nussenzweig

Research output: Contribution to journal › Article › peer-review

Abstract

Passive transfer of broadly neutralizing HIV antibodies can prevent infection, which suggests that vaccines that elicit such antibodies would be protective. Thus far, however, few broadly neutralizing HIV antibodies that occur naturally have been characterized. To determine whether these antibodies are part of a larger group of related molecules, we cloned 576 new HIV antibodies from four unrelated individuals. All four individuals produced expanded clones of potent broadly neutralizing CD4-binding-site antibodies that mimic binding to CD4. Despite extensive hypermutation, the new antibodies shared a consensus sequence of 68 immunoglobulin H (IgH) chain amino acids and arise independently from two related IgH genes. Comparison of the crystal structure of one of the antibodies to the broadly neutralizing antibody VRC01 revealed conservation of the contacts to the HIV spike.

Original language	English
Pages (from-to)	1633-1637
Number of pages	5
Journal	Science
Volume	333
Issue number	6049
DOIs	https://doi.org/10.1126/science.1207227
State	Published - 16 Sep 2011
Externally published	Yes

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Scheid, J. F., Mouquet, H., Ueberheide, B., Diskin, R., Klein, F., Oliveira, T. Y. K., Pietzsch, J., Fenyo, D., Abadir, A., Velinzon, K., Hurley, A., Myung, S., Boulad, F., Poignard, P., Burton, D. R., Pereyra, F., Ho, D. D., Walker, B. D., Seaman, M. S., ... Nussenzweig, M. C. (2011). Sequence and Structural Convergence of Broad and Potent HIV Antibodies That Mimic CD4 Binding. Science, 333(6049), 1633-1637. https://doi.org/10.1126/science.1207227

@article{a8a7424c149d4e5a8b9ea6512c761e5f,

title = "Sequence and Structural Convergence of Broad and Potent HIV Antibodies That Mimic CD4 Binding",

abstract = "Passive transfer of broadly neutralizing HIV antibodies can prevent infection, which suggests that vaccines that elicit such antibodies would be protective. Thus far, however, few broadly neutralizing HIV antibodies that occur naturally have been characterized. To determine whether these antibodies are part of a larger group of related molecules, we cloned 576 new HIV antibodies from four unrelated individuals. All four individuals produced expanded clones of potent broadly neutralizing CD4-binding-site antibodies that mimic binding to CD4. Despite extensive hypermutation, the new antibodies shared a consensus sequence of 68 immunoglobulin H (IgH) chain amino acids and arise independently from two related IgH genes. Comparison of the crystal structure of one of the antibodies to the broadly neutralizing antibody VRC01 revealed conservation of the contacts to the HIV spike.",

author = "Scheid, \{Johannes F.\} and Hugo Mouquet and Beatrix Ueberheide and Ron Diskin and Florian Klein and Oliveira, \{Thiago Y.K.\} and John Pietzsch and David Fenyo and Alexander Abadir and Klara Velinzon and Arlene Hurley and Sunnie Myung and Farid Boulad and Pascal Poignard and Burton, \{Dennis R.\} and Florencia Pereyra and Ho, \{David D.\} and Walker, \{Bruce D.\} and Seaman, \{Michael S.\} and Bjorkman, \{Pamela J.\} and Chait, \{Brian T.\} and Nussenzweig, \{Michel C.\}",

note = "NIH [P01 AI081677, RR00862, RR022220]; Bill \& Melinda Gates Foundation's Collaboration for AIDS Vaccine Discovery/Comprehensive Antibody-Vaccine Immune Monitoring Consortium [38619s, 38660]; Gordon and Betty Moore Foundation; Stanford Synchrotron Radiation Lightsource; German Research Foundation (Deutsche Forschungsgemeinschaft) [KL 2389/1-1]",

year = "2011",

month = sep,

day = "16",

doi = "10.1126/science.1207227",

language = "الإنجليزيّة",

volume = "333",

pages = "1633--1637",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

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Scheid, JF, Mouquet, H, Ueberheide, B, Diskin, R, Klein, F, Oliveira, TYK, Pietzsch, J, Fenyo, D, Abadir, A, Velinzon, K, Hurley, A, Myung, S, Boulad, F, Poignard, P, Burton, DR, Pereyra, F, Ho, DD, Walker, BD, Seaman, MS, Bjorkman, PJ, Chait, BT & Nussenzweig, MC 2011, 'Sequence and Structural Convergence of Broad and Potent HIV Antibodies That Mimic CD4 Binding', Science, vol. 333, no. 6049, pp. 1633-1637. https://doi.org/10.1126/science.1207227

TY - JOUR

T1 - Sequence and Structural Convergence of Broad and Potent HIV Antibodies That Mimic CD4 Binding

AU - Scheid, Johannes F.

AU - Mouquet, Hugo

AU - Ueberheide, Beatrix

AU - Diskin, Ron

AU - Klein, Florian

AU - Oliveira, Thiago Y.K.

AU - Pietzsch, John

AU - Fenyo, David

AU - Abadir, Alexander

AU - Velinzon, Klara

AU - Hurley, Arlene

AU - Myung, Sunnie

AU - Boulad, Farid

AU - Poignard, Pascal

AU - Burton, Dennis R.

AU - Pereyra, Florencia

AU - Ho, David D.

AU - Walker, Bruce D.

AU - Seaman, Michael S.

AU - Bjorkman, Pamela J.

AU - Chait, Brian T.

AU - Nussenzweig, Michel C.

N1 - NIH [P01 AI081677, RR00862, RR022220]; Bill & Melinda Gates Foundation's Collaboration for AIDS Vaccine Discovery/Comprehensive Antibody-Vaccine Immune Monitoring Consortium [38619s, 38660]; Gordon and Betty Moore Foundation; Stanford Synchrotron Radiation Lightsource; German Research Foundation (Deutsche Forschungsgemeinschaft) [KL 2389/1-1]

PY - 2011/9/16

Y1 - 2011/9/16

N2 - Passive transfer of broadly neutralizing HIV antibodies can prevent infection, which suggests that vaccines that elicit such antibodies would be protective. Thus far, however, few broadly neutralizing HIV antibodies that occur naturally have been characterized. To determine whether these antibodies are part of a larger group of related molecules, we cloned 576 new HIV antibodies from four unrelated individuals. All four individuals produced expanded clones of potent broadly neutralizing CD4-binding-site antibodies that mimic binding to CD4. Despite extensive hypermutation, the new antibodies shared a consensus sequence of 68 immunoglobulin H (IgH) chain amino acids and arise independently from two related IgH genes. Comparison of the crystal structure of one of the antibodies to the broadly neutralizing antibody VRC01 revealed conservation of the contacts to the HIV spike.

AB - Passive transfer of broadly neutralizing HIV antibodies can prevent infection, which suggests that vaccines that elicit such antibodies would be protective. Thus far, however, few broadly neutralizing HIV antibodies that occur naturally have been characterized. To determine whether these antibodies are part of a larger group of related molecules, we cloned 576 new HIV antibodies from four unrelated individuals. All four individuals produced expanded clones of potent broadly neutralizing CD4-binding-site antibodies that mimic binding to CD4. Despite extensive hypermutation, the new antibodies shared a consensus sequence of 68 immunoglobulin H (IgH) chain amino acids and arise independently from two related IgH genes. Comparison of the crystal structure of one of the antibodies to the broadly neutralizing antibody VRC01 revealed conservation of the contacts to the HIV spike.

UR - http://www.scopus.com/inward/record.url?scp=80052925616&partnerID=8YFLogxK

U2 - 10.1126/science.1207227

DO - 10.1126/science.1207227

M3 - مقالة

SN - 0036-8075

VL - 333

SP - 1633

EP - 1637

JO - Science

JF - Science

IS - 6049

ER -

Sequence and Structural Convergence of Broad and Potent HIV Antibodies That Mimic CD4 Binding

Abstract

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