Immunization for HIV-1 Broadly Neutralizing Antibodies in Human Ig Knockin Mice

Pia Dosenovic; Lotta von Boehmer; Amelia Escolano; Joseph Jardine; Natalia T. Freund; Alexander D. Gitlin; Andrew T. McGuire; Daniel W. Kulp; Thiago Oliveira; Louise Scharf; John Pietzsch; Matthew D. Gray; Albert Cupo; Marit J. van Gils; Kai-Hui Yao; Cassie Liu; Anna Gazumyan; Michael S. Seaman; Pamela J. Björkman; Rogier W. Sanders; John P. Moore; Leonidas Stamatatos; William R. Schief; Michel C. Nussenzweig

doi:https://doi.org/10.1016/j.cell.2015.06.003

Immunization for HIV-1 Broadly Neutralizing Antibodies in Human Ig Knockin Mice

Pia Dosenovic, Lotta von Boehmer, Amelia Escolano, Joseph Jardine, Natalia T. Freund, Alexander D. Gitlin, Andrew T. McGuire, Daniel W. Kulp, Thiago Oliveira, Louise Scharf, John Pietzsch, Matthew D. Gray, Albert Cupo, Marit J. van Gils, Kai-Hui Yao, Cassie Liu, Anna Gazumyan, Michael S. Seaman, Pamela J. Björkman, Rogier W. SandersJohn P. Moore, Leonidas Stamatatos, William R. Schief, Michel C. Nussenzweig

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

207 Citations (Scopus)

Abstract

A subset of individuals infected with HIV-1 develops broadly neutralizing antibodies (bNAbs) that can prevent infection, but it has not yet been possible to elicit these antibodies by immunization. To systematically explore how immunization might be tailored to produce them, we generated mice expressing the predicted germline or mature heavy chains of a potent bNAb to the CD4 binding site (CD4bs) on the HIV-1 envelope glycoprotein (Env). Immunogens specifically designed to activate B cells bearing germline antibodies are required to initiate immune responses, but they do not elicit bNAbs. In contrast, native-like Env trimers fail to activate B cells expressing germline antibodies but elicit bNAbs by selecting for a restricted group of light chains bearing specific somatic mutations that enhance neutralizing activity. The data suggest that vaccination to elicit anti-HIV-1 antibodies will require immunization with a succession of related immunogens

Original language	English
Pages (from-to)	1505-1515
Journal	Cell
Volume	161
Issue number	7
DOIs	https://doi.org/10.1016/j.cell.2015.06.003
Publication status	Published - 2015

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Cite this

Dosenovic, P., von Boehmer, L., Escolano, A., Jardine, J., Freund, N. T., Gitlin, A. D., McGuire, A. T., Kulp, D. W., Oliveira, T., Scharf, L., Pietzsch, J., Gray, M. D., Cupo, A., van Gils, M. J., Yao, K.-H., Liu, C., Gazumyan, A., Seaman, M. S., Björkman, P. J., ... Nussenzweig, M. C. (2015). Immunization for HIV-1 Broadly Neutralizing Antibodies in Human Ig Knockin Mice. Cell, 161(7), 1505-1515. https://doi.org/10.1016/j.cell.2015.06.003

@article{e8c493ee394e4e81926418433beaa43a,

title = "Immunization for HIV-1 Broadly Neutralizing Antibodies in Human Ig Knockin Mice",

abstract = "A subset of individuals infected with HIV-1 develops broadly neutralizing antibodies (bNAbs) that can prevent infection, but it has not yet been possible to elicit these antibodies by immunization. To systematically explore how immunization might be tailored to produce them, we generated mice expressing the predicted germline or mature heavy chains of a potent bNAb to the CD4 binding site (CD4bs) on the HIV-1 envelope glycoprotein (Env). Immunogens specifically designed to activate B cells bearing germline antibodies are required to initiate immune responses, but they do not elicit bNAbs. In contrast, native-like Env trimers fail to activate B cells expressing germline antibodies but elicit bNAbs by selecting for a restricted group of light chains bearing specific somatic mutations that enhance neutralizing activity. The data suggest that vaccination to elicit anti-HIV-1 antibodies will require immunization with a succession of related immunogens",

author = "Pia Dosenovic and {von Boehmer}, Lotta and Amelia Escolano and Joseph Jardine and Freund, {Natalia T.} and Gitlin, {Alexander D.} and McGuire, {Andrew T.} and Kulp, {Daniel W.} and Thiago Oliveira and Louise Scharf and John Pietzsch and Gray, {Matthew D.} and Albert Cupo and {van Gils}, {Marit J.} and Kai-Hui Yao and Cassie Liu and Anna Gazumyan and Seaman, {Michael S.} and Bj{\"o}rkman, {Pamela J.} and Sanders, {Rogier W.} and Moore, {John P.} and Leonidas Stamatatos and Schief, {William R.} and Nussenzweig, {Michel C.}",

year = "2015",

doi = "https://doi.org/10.1016/j.cell.2015.06.003",

language = "English",

volume = "161",

pages = "1505--1515",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

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Dosenovic, P, von Boehmer, L, Escolano, A, Jardine, J, Freund, NT, Gitlin, AD, McGuire, AT, Kulp, DW, Oliveira, T, Scharf, L, Pietzsch, J, Gray, MD, Cupo, A, van Gils, MJ, Yao, K-H, Liu, C, Gazumyan, A, Seaman, MS, Björkman, PJ, Sanders, RW, Moore, JP, Stamatatos, L, Schief, WR & Nussenzweig, MC 2015, 'Immunization for HIV-1 Broadly Neutralizing Antibodies in Human Ig Knockin Mice', Cell, vol. 161, no. 7, pp. 1505-1515. https://doi.org/10.1016/j.cell.2015.06.003

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AU - Dosenovic, Pia

AU - von Boehmer, Lotta

AU - Escolano, Amelia

AU - Jardine, Joseph

AU - Freund, Natalia T.

AU - Gitlin, Alexander D.

AU - McGuire, Andrew T.

AU - Kulp, Daniel W.

AU - Oliveira, Thiago

AU - Scharf, Louise

AU - Pietzsch, John

AU - Gray, Matthew D.

AU - Cupo, Albert

AU - van Gils, Marit J.

AU - Yao, Kai-Hui

AU - Liu, Cassie

AU - Gazumyan, Anna

AU - Seaman, Michael S.

AU - Björkman, Pamela J.

AU - Sanders, Rogier W.

AU - Moore, John P.

AU - Stamatatos, Leonidas

AU - Schief, William R.

AU - Nussenzweig, Michel C.

PY - 2015

Y1 - 2015

N2 - A subset of individuals infected with HIV-1 develops broadly neutralizing antibodies (bNAbs) that can prevent infection, but it has not yet been possible to elicit these antibodies by immunization. To systematically explore how immunization might be tailored to produce them, we generated mice expressing the predicted germline or mature heavy chains of a potent bNAb to the CD4 binding site (CD4bs) on the HIV-1 envelope glycoprotein (Env). Immunogens specifically designed to activate B cells bearing germline antibodies are required to initiate immune responses, but they do not elicit bNAbs. In contrast, native-like Env trimers fail to activate B cells expressing germline antibodies but elicit bNAbs by selecting for a restricted group of light chains bearing specific somatic mutations that enhance neutralizing activity. The data suggest that vaccination to elicit anti-HIV-1 antibodies will require immunization with a succession of related immunogens

AB - A subset of individuals infected with HIV-1 develops broadly neutralizing antibodies (bNAbs) that can prevent infection, but it has not yet been possible to elicit these antibodies by immunization. To systematically explore how immunization might be tailored to produce them, we generated mice expressing the predicted germline or mature heavy chains of a potent bNAb to the CD4 binding site (CD4bs) on the HIV-1 envelope glycoprotein (Env). Immunogens specifically designed to activate B cells bearing germline antibodies are required to initiate immune responses, but they do not elicit bNAbs. In contrast, native-like Env trimers fail to activate B cells expressing germline antibodies but elicit bNAbs by selecting for a restricted group of light chains bearing specific somatic mutations that enhance neutralizing activity. The data suggest that vaccination to elicit anti-HIV-1 antibodies will require immunization with a succession of related immunogens

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DO - https://doi.org/10.1016/j.cell.2015.06.003

M3 - Article

C2 - 26091035

SN - 0092-8674

VL - 161

SP - 1505

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JO - Cell

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