Holes in the Glycan Shield of the Native HIV Envelope Are a Target of Trimer-Elicited Neutralizing Antibodies

Laura E. McCoy; Marit J. van Gils; Gabriel Ozorowski; Terrence Messmer; Bryan Briney; James E. Voss; Daniel W. Kulp; Matthew S. Macauley; Devin Sok; Matthias Pauthner; Sergey Menis; Christopher A. Cottrell; Jonathan L. Torres; Jessica Hsueh; William R. Schief; Ian A. Wilson; Andrew B. Ward; Rogier W. Sanders; Dennis R. Burton

doi:https://doi.org/10.1016/j.celrep.2016.07.074

Holes in the Glycan Shield of the Native HIV Envelope Are a Target of Trimer-Elicited Neutralizing Antibodies

Laura E. McCoy, Marit J. van Gils, Gabriel Ozorowski, Terrence Messmer, Bryan Briney, James E. Voss, Daniel W. Kulp, Matthew S. Macauley, Devin Sok, Matthias Pauthner, Sergey Menis, Christopher A. Cottrell, Jonathan L. Torres, Jessica Hsueh, William R. Schief, Ian A. Wilson, Andrew B. Ward, Rogier W. Sanders, Dennis R. Burton

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

170 Citations (Scopus)

Abstract

A major advance in the search for an HIV vaccine has been the development of a near-native Envelope trimer (BG505 SOSIP.664) that can induce robust autologous Tier 2 neutralization. Here, potently neutralizing monoclonal antibodies (nAbs) from rabbits immunized with BG505 SOSIP.664 are shown to recognize an immunodominant region of gp120 centered on residue 241. Residue 241 occupies a hole in the glycan defenses of the BG505 isolate, with fewer than 3% of global isolates lacking a glycan site at this position. However, at least one conserved glycan site is missing in 89% of viruses, suggesting the presence of glycan holes in most HIV isolates. Serum evidence is consistent with targeting of holes in natural infection. The immunogenic nature of breaches in the glycan shield has been under-appreciated in previous attempts to understand autologous neutralizing antibody responses and has important potential consequences for HIV vaccine design

Original language	English
Pages (from-to)	2327-2338
Journal	Cell reports
Volume	16
Issue number	9
DOIs	https://doi.org/10.1016/j.celrep.2016.07.074
Publication status	Published - 2016

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https://doi.org/10.1016/j.celrep.2016.07.074

Cite this

McCoy, L. E., van Gils, M. J., Ozorowski, G., Messmer, T., Briney, B., Voss, J. E., Kulp, D. W., Macauley, M. S., Sok, D., Pauthner, M., Menis, S., Cottrell, C. A., Torres, J. L., Hsueh, J., Schief, W. R., Wilson, I. A., Ward, A. B., Sanders, R. W., & Burton, D. R. (2016). Holes in the Glycan Shield of the Native HIV Envelope Are a Target of Trimer-Elicited Neutralizing Antibodies. Cell reports, 16(9), 2327-2338. https://doi.org/10.1016/j.celrep.2016.07.074

@article{46311de8a28347e1b8f242f1a21acc1e,

title = "Holes in the Glycan Shield of the Native HIV Envelope Are a Target of Trimer-Elicited Neutralizing Antibodies",

abstract = "A major advance in the search for an HIV vaccine has been the development of a near-native Envelope trimer (BG505 SOSIP.664) that can induce robust autologous Tier 2 neutralization. Here, potently neutralizing monoclonal antibodies (nAbs) from rabbits immunized with BG505 SOSIP.664 are shown to recognize an immunodominant region of gp120 centered on residue 241. Residue 241 occupies a hole in the glycan defenses of the BG505 isolate, with fewer than 3% of global isolates lacking a glycan site at this position. However, at least one conserved glycan site is missing in 89% of viruses, suggesting the presence of glycan holes in most HIV isolates. Serum evidence is consistent with targeting of holes in natural infection. The immunogenic nature of breaches in the glycan shield has been under-appreciated in previous attempts to understand autologous neutralizing antibody responses and has important potential consequences for HIV vaccine design",

author = "McCoy, {Laura E.} and {van Gils}, {Marit J.} and Gabriel Ozorowski and Terrence Messmer and Bryan Briney and Voss, {James E.} and Kulp, {Daniel W.} and Macauley, {Matthew S.} and Devin Sok and Matthias Pauthner and Sergey Menis and Cottrell, {Christopher A.} and Torres, {Jonathan L.} and Jessica Hsueh and Schief, {William R.} and Wilson, {Ian A.} and Ward, {Andrew B.} and Sanders, {Rogier W.} and Burton, {Dennis R.}",

year = "2016",

doi = "https://doi.org/10.1016/j.celrep.2016.07.074",

language = "English",

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pages = "2327--2338",

journal = "Cell reports",

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McCoy, LE, van Gils, MJ, Ozorowski, G, Messmer, T, Briney, B, Voss, JE, Kulp, DW, Macauley, MS, Sok, D, Pauthner, M, Menis, S, Cottrell, CA, Torres, JL, Hsueh, J, Schief, WR, Wilson, IA, Ward, AB, Sanders, RW & Burton, DR 2016, 'Holes in the Glycan Shield of the Native HIV Envelope Are a Target of Trimer-Elicited Neutralizing Antibodies', Cell reports, vol. 16, no. 9, pp. 2327-2338. https://doi.org/10.1016/j.celrep.2016.07.074

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T1 - Holes in the Glycan Shield of the Native HIV Envelope Are a Target of Trimer-Elicited Neutralizing Antibodies

AU - McCoy, Laura E.

AU - van Gils, Marit J.

AU - Ozorowski, Gabriel

AU - Messmer, Terrence

AU - Briney, Bryan

AU - Voss, James E.

AU - Kulp, Daniel W.

AU - Macauley, Matthew S.

AU - Sok, Devin

AU - Pauthner, Matthias

AU - Menis, Sergey

AU - Cottrell, Christopher A.

AU - Torres, Jonathan L.

AU - Hsueh, Jessica

AU - Schief, William R.

AU - Wilson, Ian A.

AU - Ward, Andrew B.

AU - Sanders, Rogier W.

AU - Burton, Dennis R.

PY - 2016

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N2 - A major advance in the search for an HIV vaccine has been the development of a near-native Envelope trimer (BG505 SOSIP.664) that can induce robust autologous Tier 2 neutralization. Here, potently neutralizing monoclonal antibodies (nAbs) from rabbits immunized with BG505 SOSIP.664 are shown to recognize an immunodominant region of gp120 centered on residue 241. Residue 241 occupies a hole in the glycan defenses of the BG505 isolate, with fewer than 3% of global isolates lacking a glycan site at this position. However, at least one conserved glycan site is missing in 89% of viruses, suggesting the presence of glycan holes in most HIV isolates. Serum evidence is consistent with targeting of holes in natural infection. The immunogenic nature of breaches in the glycan shield has been under-appreciated in previous attempts to understand autologous neutralizing antibody responses and has important potential consequences for HIV vaccine design

AB - A major advance in the search for an HIV vaccine has been the development of a near-native Envelope trimer (BG505 SOSIP.664) that can induce robust autologous Tier 2 neutralization. Here, potently neutralizing monoclonal antibodies (nAbs) from rabbits immunized with BG505 SOSIP.664 are shown to recognize an immunodominant region of gp120 centered on residue 241. Residue 241 occupies a hole in the glycan defenses of the BG505 isolate, with fewer than 3% of global isolates lacking a glycan site at this position. However, at least one conserved glycan site is missing in 89% of viruses, suggesting the presence of glycan holes in most HIV isolates. Serum evidence is consistent with targeting of holes in natural infection. The immunogenic nature of breaches in the glycan shield has been under-appreciated in previous attempts to understand autologous neutralizing antibody responses and has important potential consequences for HIV vaccine design

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DO - https://doi.org/10.1016/j.celrep.2016.07.074

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