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Enhancing glycan occupancy of soluble HIV-1 envelope trimers to mimic the native viral spike. / Derking, Ronald; Allen, Joel D.; Cottrell, Christopher A. et al.

In: Cell reports, Vol. 35, No. 1, 108933, 06.04.2021.

Research output: Contribution to journalArticleAcademicpeer-review

Harvard

Derking, R, Allen, JD, Cottrell, CA, Sliepen, K, Seabright, GE, Lee, W-H, Aldon, Y, Rantalainen, K, Antanasijevic, A, Copps, J, Yasmeen, A, Cupo, A, Cruz Portillo, VM, Poniman, M, Bol, N, van der Woude, P, de Taeye, SW, van den Kerkhof, TLGM, Klasse, PJ, Ozorowski, G, van Gils, MJ, Moore, JP, Ward, AB, Crispin, M & Sanders, RW 2021, 'Enhancing glycan occupancy of soluble HIV-1 envelope trimers to mimic the native viral spike', Cell reports, vol. 35, no. 1, 108933. https://doi.org/10.1101/2020.07.02.184135, https://doi.org/10.1016/j.celrep.2021.108933

APA

Derking, R., Allen, J. D., Cottrell, C. A., Sliepen, K., Seabright, G. E., Lee, W-H., Aldon, Y., Rantalainen, K., Antanasijevic, A., Copps, J., Yasmeen, A., Cupo, A., Cruz Portillo, V. M., Poniman, M., Bol, N., van der Woude, P., de Taeye, S. W., van den Kerkhof, T. L. G. M., Klasse, P. J., ... Sanders, R. W. (2021). Enhancing glycan occupancy of soluble HIV-1 envelope trimers to mimic the native viral spike. Cell reports, 35(1), [108933]. https://doi.org/10.1101/2020.07.02.184135, https://doi.org/10.1016/j.celrep.2021.108933

Vancouver

Author

Derking, Ronald ; Allen, Joel D. ; Cottrell, Christopher A. et al. / Enhancing glycan occupancy of soluble HIV-1 envelope trimers to mimic the native viral spike. In: Cell reports. 2021 ; Vol. 35, No. 1.

BibTeX

@article{c2cd210f205745079ad4cb4db858e71d,
title = "Enhancing glycan occupancy of soluble HIV-1 envelope trimers to mimic the native viral spike",
abstract = "Artificial glycan holes on recombinant Env-based vaccines occur when a potential N-linked glycosylation site (PNGS) is under-occupied, but not on their viral counterparts. Native-like SOSIP trimers, including clinical candidates, contain such holes in the glycan shield that induce strain-specific neutralizing antibodies (NAbs) or non-NAbs. To eliminate glycan holes and mimic the glycosylation of native BG505 Env, we replace all 12 NxS sequons on BG505 SOSIP with NxT. All PNGS, except N133 and N160, are nearly fully occupied. Occupancy of the N133 site is increased by changing N133 to NxS, whereas occupancy of the N160 site is restored by reverting the nearby N156 sequon to NxS. Hence, PNGS in close proximity, such as in the N133-N137 and N156-N160 pairs, affect each other's occupancy. We further apply this approach to improve the occupancy of several Env strains. Increasing glycan occupancy should reduce off-target immune responses to vaccine antigens.",
keywords = "HIV-1 vaccine research, cryo-EM, glycan occupancy, mass spectrometry",
author = "Ronald Derking and Allen, {Joel D.} and Cottrell, {Christopher A.} and Kwinten Sliepen and Seabright, {Gemma E.} and Wen-Hsin Lee and Yoann Aldon and Kimmo Rantalainen and Aleksandar Antanasijevic and Jeffrey Copps and Anila Yasmeen and Albert Cupo and {Cruz Portillo}, {Victor M.} and Meliawati Poniman and Niki Bol and {van der Woude}, Patricia and {de Taeye}, {Steven W.} and {van den Kerkhof}, {Tom L. G. M.} and Klasse, {P. J.} and Gabriel Ozorowski and {van Gils}, {Marit J.} and Moore, {John P.} and Ward, {Andrew B.} and Max Crispin and Sanders, {Rogier W.}",
note = "Publisher Copyright: {\textcopyright} 2021 The Author(s) Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
month = apr,
day = "6",
doi = "10.1101/2020.07.02.184135",
language = "English",
volume = "35",
journal = "Cell reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "1",

}

RIS

TY - JOUR

T1 - Enhancing glycan occupancy of soluble HIV-1 envelope trimers to mimic the native viral spike

AU - Derking, Ronald

AU - Allen, Joel D.

AU - Cottrell, Christopher A.

AU - Sliepen, Kwinten

AU - Seabright, Gemma E.

AU - Lee, Wen-Hsin

AU - Aldon, Yoann

AU - Rantalainen, Kimmo

AU - Antanasijevic, Aleksandar

AU - Copps, Jeffrey

AU - Yasmeen, Anila

AU - Cupo, Albert

AU - Cruz Portillo, Victor M.

AU - Poniman, Meliawati

AU - Bol, Niki

AU - van der Woude, Patricia

AU - de Taeye, Steven W.

AU - van den Kerkhof, Tom L. G. M.

AU - Klasse, P. J.

AU - Ozorowski, Gabriel

AU - van Gils, Marit J.

AU - Moore, John P.

AU - Ward, Andrew B.

AU - Crispin, Max

AU - Sanders, Rogier W.

N1 - Publisher Copyright: © 2021 The Author(s) Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/4/6

Y1 - 2021/4/6

N2 - Artificial glycan holes on recombinant Env-based vaccines occur when a potential N-linked glycosylation site (PNGS) is under-occupied, but not on their viral counterparts. Native-like SOSIP trimers, including clinical candidates, contain such holes in the glycan shield that induce strain-specific neutralizing antibodies (NAbs) or non-NAbs. To eliminate glycan holes and mimic the glycosylation of native BG505 Env, we replace all 12 NxS sequons on BG505 SOSIP with NxT. All PNGS, except N133 and N160, are nearly fully occupied. Occupancy of the N133 site is increased by changing N133 to NxS, whereas occupancy of the N160 site is restored by reverting the nearby N156 sequon to NxS. Hence, PNGS in close proximity, such as in the N133-N137 and N156-N160 pairs, affect each other's occupancy. We further apply this approach to improve the occupancy of several Env strains. Increasing glycan occupancy should reduce off-target immune responses to vaccine antigens.

AB - Artificial glycan holes on recombinant Env-based vaccines occur when a potential N-linked glycosylation site (PNGS) is under-occupied, but not on their viral counterparts. Native-like SOSIP trimers, including clinical candidates, contain such holes in the glycan shield that induce strain-specific neutralizing antibodies (NAbs) or non-NAbs. To eliminate glycan holes and mimic the glycosylation of native BG505 Env, we replace all 12 NxS sequons on BG505 SOSIP with NxT. All PNGS, except N133 and N160, are nearly fully occupied. Occupancy of the N133 site is increased by changing N133 to NxS, whereas occupancy of the N160 site is restored by reverting the nearby N156 sequon to NxS. Hence, PNGS in close proximity, such as in the N133-N137 and N156-N160 pairs, affect each other's occupancy. We further apply this approach to improve the occupancy of several Env strains. Increasing glycan occupancy should reduce off-target immune responses to vaccine antigens.

KW - HIV-1 vaccine research

KW - cryo-EM

KW - glycan occupancy

KW - mass spectrometry

UR - http://www.scopus.com/inward/record.url?scp=85103764117&partnerID=8YFLogxK

U2 - 10.1101/2020.07.02.184135

DO - 10.1101/2020.07.02.184135

M3 - Article

C2 - 33826885

VL - 35

JO - Cell reports

JF - Cell reports

SN - 2211-1247

IS - 1

M1 - 108933

ER -

ID: 15241691