HIV-1 neutralizing antibodies induced by native-like envelope trimers

Rogier W. Sanders; Marit J. van Gils; Ronald Derking; Devin Sok; Thomas J. Ketas; Judith A. Burger; Gabriel Ozorowski; Albert Cupo; Cassandra Simonich; Leslie Goo; Heather Arendt; Helen J. Kim; Jeong Hyun Lee; Pavel Pugach; Melissa Williams; Gargi Debnath; Brian Moldt; Mariëlle J. van Breemen; Gözde Isik; Max Medina-Ramírez; Jaap Willem Back; Wayne C. Koff; Jean-Philippe Julien; Eva G. Rakasz; Michael S. Seaman; Miklos Guttman; Kelly K. Lee; Per Johan Klasse; Celia Labranche; William R. Schief; Ian A. Wilson; Julie Overbaugh; Dennis R. Burton; Andrew B. Ward; David C. Montefiori; Hansi Dean; John P. Moore

doi:https://doi.org/10.1126/science.aac4223

HIV-1 neutralizing antibodies induced by native-like envelope trimers

Rogier W. Sanders, Marit J. van Gils, Ronald Derking, Devin Sok, Thomas J. Ketas, Judith A. Burger, Gabriel Ozorowski, Albert Cupo, Cassandra Simonich, Leslie Goo, Heather Arendt, Helen J. Kim, Jeong Hyun Lee, Pavel Pugach, Melissa Williams, Gargi Debnath, Brian Moldt, Mariëlle J. van Breemen, Gözde Isik, Max Medina-RamírezJaap Willem Back, Wayne C. Koff, Jean-Philippe Julien, Eva G. Rakasz, Michael S. Seaman, Miklos Guttman, Kelly K. Lee, Per Johan Klasse, Celia Labranche, William R. Schief, Ian A. Wilson, Julie Overbaugh, Dennis R. Burton, Andrew B. Ward, David C. Montefiori, Hansi Dean, John P. Moore

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

408 Citations (Scopus)

Abstract

A challenge for HIV-1 immunogen design is the difficulty of inducing neutralizing antibodies (NAbs) against neutralization-resistant (tier 2) viruses that dominate human transmissions. We show that a soluble recombinant HIV-1 envelope glycoprotein trimer that adopts a native conformation, BG505 SOSIP.664, induced NAbs potently against the sequence-matched tier 2 virus in rabbits and similar but weaker responses in macaques. The trimer also consistently induced cross-reactive NAbs against more sensitive (tier 1) viruses. Tier 2 NAbs recognized conformational epitopes that differed between animals and in some cases overlapped with those recognized by broadly neutralizing antibodies (bNAbs), whereas tier 1 responses targeted linear V3 epitopes. A second trimer, B41 SOSIP. 664, also induced a strong autologous tier 2 NAb response in rabbits. Thus, native-like trimers represent a promising starting point for the development of HIV-1 vaccines aimed at inducing bNAbs

Original language	English
Pages (from-to)	aac4223-154
Journal	Science
Volume	349
Issue number	6244
DOIs	https://doi.org/10.1126/science.aac4223
Publication status	Published - 2015

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https://doi.org/10.1126/science.aac4223

Cite this

Sanders, R. W., van Gils, M. J., Derking, R., Sok, D., Ketas, T. J., Burger, J. A., Ozorowski, G., Cupo, A., Simonich, C., Goo, L., Arendt, H., Kim, H. J., Lee, J. H., Pugach, P., Williams, M., Debnath, G., Moldt, B., van Breemen, M. J., Isik, G., ... Moore, J. P. (2015). HIV-1 neutralizing antibodies induced by native-like envelope trimers. Science, 349(6244), aac4223-154. https://doi.org/10.1126/science.aac4223

@article{7802d7b7432a4201b91c156b8bb050e5,

title = "HIV-1 neutralizing antibodies induced by native-like envelope trimers",

abstract = "A challenge for HIV-1 immunogen design is the difficulty of inducing neutralizing antibodies (NAbs) against neutralization-resistant (tier 2) viruses that dominate human transmissions. We show that a soluble recombinant HIV-1 envelope glycoprotein trimer that adopts a native conformation, BG505 SOSIP.664, induced NAbs potently against the sequence-matched tier 2 virus in rabbits and similar but weaker responses in macaques. The trimer also consistently induced cross-reactive NAbs against more sensitive (tier 1) viruses. Tier 2 NAbs recognized conformational epitopes that differed between animals and in some cases overlapped with those recognized by broadly neutralizing antibodies (bNAbs), whereas tier 1 responses targeted linear V3 epitopes. A second trimer, B41 SOSIP. 664, also induced a strong autologous tier 2 NAb response in rabbits. Thus, native-like trimers represent a promising starting point for the development of HIV-1 vaccines aimed at inducing bNAbs",

author = "Sanders, {Rogier W.} and {van Gils}, {Marit J.} and Ronald Derking and Devin Sok and Ketas, {Thomas J.} and Burger, {Judith A.} and Gabriel Ozorowski and Albert Cupo and Cassandra Simonich and Leslie Goo and Heather Arendt and Kim, {Helen J.} and Lee, {Jeong Hyun} and Pavel Pugach and Melissa Williams and Gargi Debnath and Brian Moldt and {van Breemen}, {Mari{\"e}lle J.} and G{\"o}zde Isik and Max Medina-Ram{\'i}rez and Back, {Jaap Willem} and Koff, {Wayne C.} and Jean-Philippe Julien and Rakasz, {Eva G.} and Seaman, {Michael S.} and Miklos Guttman and Lee, {Kelly K.} and Klasse, {Per Johan} and Celia Labranche and Schief, {William R.} and Wilson, {Ian A.} and Julie Overbaugh and Burton, {Dennis R.} and Ward, {Andrew B.} and Montefiori, {David C.} and Hansi Dean and Moore, {John P.}",

year = "2015",

doi = "https://doi.org/10.1126/science.aac4223",

language = "English",

volume = "349",

pages = "aac4223--154",

journal = "Science",

issn = "0036-8075",

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Sanders, RW , van Gils, MJ, Derking, R, Sok, D, Ketas, TJ, Burger, JA, Ozorowski, G, Cupo, A, Simonich, C, Goo, L, Arendt, H, Kim, HJ, Lee, JH, Pugach, P, Williams, M, Debnath, G, Moldt, B, van Breemen, MJ, Isik, G, Medina-Ramírez, M, Back, JW, Koff, WC, Julien, J-P, Rakasz, EG, Seaman, MS, Guttman, M, Lee, KK, Klasse, PJ, Labranche, C, Schief, WR, Wilson, IA, Overbaugh, J, Burton, DR, Ward, AB, Montefiori, DC, Dean, H & Moore, JP 2015, 'HIV-1 neutralizing antibodies induced by native-like envelope trimers', Science, vol. 349, no. 6244, pp. aac4223-154. https://doi.org/10.1126/science.aac4223

TY - JOUR

T1 - HIV-1 neutralizing antibodies induced by native-like envelope trimers

AU - Sanders, Rogier W.

AU - van Gils, Marit J.

AU - Derking, Ronald

AU - Sok, Devin

AU - Ketas, Thomas J.

AU - Burger, Judith A.

AU - Ozorowski, Gabriel

AU - Cupo, Albert

AU - Simonich, Cassandra

AU - Goo, Leslie

AU - Arendt, Heather

AU - Kim, Helen J.

AU - Lee, Jeong Hyun

AU - Pugach, Pavel

AU - Williams, Melissa

AU - Debnath, Gargi

AU - Moldt, Brian

AU - van Breemen, Mariëlle J.

AU - Isik, Gözde

AU - Medina-Ramírez, Max

AU - Back, Jaap Willem

AU - Koff, Wayne C.

AU - Julien, Jean-Philippe

AU - Rakasz, Eva G.

AU - Seaman, Michael S.

AU - Guttman, Miklos

AU - Lee, Kelly K.

AU - Klasse, Per Johan

AU - Labranche, Celia

AU - Schief, William R.

AU - Wilson, Ian A.

AU - Overbaugh, Julie

AU - Burton, Dennis R.

AU - Ward, Andrew B.

AU - Montefiori, David C.

AU - Dean, Hansi

AU - Moore, John P.

PY - 2015

Y1 - 2015

N2 - A challenge for HIV-1 immunogen design is the difficulty of inducing neutralizing antibodies (NAbs) against neutralization-resistant (tier 2) viruses that dominate human transmissions. We show that a soluble recombinant HIV-1 envelope glycoprotein trimer that adopts a native conformation, BG505 SOSIP.664, induced NAbs potently against the sequence-matched tier 2 virus in rabbits and similar but weaker responses in macaques. The trimer also consistently induced cross-reactive NAbs against more sensitive (tier 1) viruses. Tier 2 NAbs recognized conformational epitopes that differed between animals and in some cases overlapped with those recognized by broadly neutralizing antibodies (bNAbs), whereas tier 1 responses targeted linear V3 epitopes. A second trimer, B41 SOSIP. 664, also induced a strong autologous tier 2 NAb response in rabbits. Thus, native-like trimers represent a promising starting point for the development of HIV-1 vaccines aimed at inducing bNAbs

AB - A challenge for HIV-1 immunogen design is the difficulty of inducing neutralizing antibodies (NAbs) against neutralization-resistant (tier 2) viruses that dominate human transmissions. We show that a soluble recombinant HIV-1 envelope glycoprotein trimer that adopts a native conformation, BG505 SOSIP.664, induced NAbs potently against the sequence-matched tier 2 virus in rabbits and similar but weaker responses in macaques. The trimer also consistently induced cross-reactive NAbs against more sensitive (tier 1) viruses. Tier 2 NAbs recognized conformational epitopes that differed between animals and in some cases overlapped with those recognized by broadly neutralizing antibodies (bNAbs), whereas tier 1 responses targeted linear V3 epitopes. A second trimer, B41 SOSIP. 664, also induced a strong autologous tier 2 NAb response in rabbits. Thus, native-like trimers represent a promising starting point for the development of HIV-1 vaccines aimed at inducing bNAbs

U2 - https://doi.org/10.1126/science.aac4223

DO - https://doi.org/10.1126/science.aac4223

M3 - Article

C2 - 26089353

SN - 0036-8075

VL - 349

SP - aac4223-154

JO - Science

JF - Science

IS - 6244

ER -