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: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 › peer-review

Abstract

Summary 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
Number of pages	11
Journal	Cell
Volume	161
Issue number	7
DOIs	https://doi.org/10.1016/j.cell.2015.06.003
State	Published - 20 Jun 2015
Externally published	Yes

All Science Journal Classification (ASJC) codes

General Biochemistry,Genetics and Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.cell.2015.06.003

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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{dc3577f4f23c4726883981ebdec31054,

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

abstract = "Summary 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 Yao, {Kai Hui} 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.}",

note = "Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",

year = "2015",

month = jun,

day = "20",

doi = "10.1016/j.cell.2015.06.003",

language = "الإنجليزيّة",

volume = "161",

pages = "1505--1515",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

number = "7",

}

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, KH, 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

TY - JOUR

T1 - Immunization for HIV-1 Broadly Neutralizing Antibodies in Human Ig Knockin Mice

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 - 2015/6/20

Y1 - 2015/6/20

N2 - Summary 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 - Summary 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.

UR - http://www.scopus.com/inward/record.url?scp=84934937791&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2015.06.003

DO - 10.1016/j.cell.2015.06.003

M3 - مقالة

SN - 0092-8674

VL - 161

SP - 1505

EP - 1515

JO - Cell

JF - Cell

IS - 7

ER -

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

Abstract

All Science Journal Classification (ASJC) codes

UN SDGs

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