Affinity Maturation of a Potent Family of HIV Antibodies Is Primarily Focused on Accommodating or Avoiding Glycans

Fernando Garces; Jeong Hyun Lee; Natalia de Val; Alba Torrents de la Pena; Leopold Kong; Cristina Puchades; Yuanzi Hua; Robyn L. Stanfield; Dennis R. Burton; John P. Moore; Rogier W. Sanders; Andrew B. Ward; Ian A. Wilson

doi:https://doi.org/10.1016/j.immuni.2015.11.007

Affinity Maturation of a Potent Family of HIV Antibodies Is Primarily Focused on Accommodating or Avoiding Glycans

Fernando Garces, Jeong Hyun Lee, Natalia de Val, Alba Torrents de la Pena, Leopold Kong, Cristina Puchades, Yuanzi Hua, Robyn L. Stanfield, Dennis R. Burton, John P. Moore, Rogier W. Sanders, Andrew B. Ward, Ian A. Wilson

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

166 Citations (Scopus)

Abstract

The high-mannose patch on the HIV-1 envelope (Env) glycoprotein is the epicenter for binding of the potent broadly neutralizing PGT121 family of antibodies, but strategies for generating such antibodies by vaccination have not been defined. We generated structures of inferred antibody intermediates by X-ray crystallography and electron microscopy to elucidate the molecular events that occurred during evolution of this family. Binding analyses revealed that affinity maturation was primarily focused on avoiding, accommodating, or binding the N137 glycan. The overall antibody approach angle to Env was defined very early in the maturation process, yet some variation evolved in the PGT121 family branches that led to differences in glycan specificities in their respective epitopes. Furthermore, we determined a crystal structure of the recombinant BG505 SOSIP.664 HIV-1 trimer with a PGT121 family member at 3.0 Å that, in concert with these antibody intermediate structures, provides insights to advance design of HIV vaccine candidates

Original language	English
Pages (from-to)	1053-1063
Journal	Immunity
Volume	43
Issue number	6
DOIs	https://doi.org/10.1016/j.immuni.2015.11.007
Publication status	Published - 2015

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https://doi.org/10.1016/j.immuni.2015.11.007

Cite this

Garces, F., Lee, J. H., de Val, N., de la Pena, A. T., Kong, L., Puchades, C., Hua, Y., Stanfield, R. L., Burton, D. R., Moore, J. P., Sanders, R. W., Ward, A. B., & Wilson, I. A. (2015). Affinity Maturation of a Potent Family of HIV Antibodies Is Primarily Focused on Accommodating or Avoiding Glycans. Immunity, 43(6), 1053-1063. https://doi.org/10.1016/j.immuni.2015.11.007

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title = "Affinity Maturation of a Potent Family of HIV Antibodies Is Primarily Focused on Accommodating or Avoiding Glycans",

abstract = "The high-mannose patch on the HIV-1 envelope (Env) glycoprotein is the epicenter for binding of the potent broadly neutralizing PGT121 family of antibodies, but strategies for generating such antibodies by vaccination have not been defined. We generated structures of inferred antibody intermediates by X-ray crystallography and electron microscopy to elucidate the molecular events that occurred during evolution of this family. Binding analyses revealed that affinity maturation was primarily focused on avoiding, accommodating, or binding the N137 glycan. The overall antibody approach angle to Env was defined very early in the maturation process, yet some variation evolved in the PGT121 family branches that led to differences in glycan specificities in their respective epitopes. Furthermore, we determined a crystal structure of the recombinant BG505 SOSIP.664 HIV-1 trimer with a PGT121 family member at 3.0 {\AA} that, in concert with these antibody intermediate structures, provides insights to advance design of HIV vaccine candidates",

author = "Fernando Garces and Lee, {Jeong Hyun} and {de Val}, Natalia and {de la Pena}, {Alba Torrents} and Leopold Kong and Cristina Puchades and Yuanzi Hua and Stanfield, {Robyn L.} and Burton, {Dennis R.} and Moore, {John P.} and Sanders, {Rogier W.} and Ward, {Andrew B.} and Wilson, {Ian A.}",

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AU - de la Pena, Alba Torrents

AU - Kong, Leopold

AU - Puchades, Cristina

AU - Hua, Yuanzi

AU - Stanfield, Robyn L.

AU - Burton, Dennis R.

AU - Moore, John P.

AU - Sanders, Rogier W.

AU - Ward, Andrew B.

AU - Wilson, Ian A.

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AB - The high-mannose patch on the HIV-1 envelope (Env) glycoprotein is the epicenter for binding of the potent broadly neutralizing PGT121 family of antibodies, but strategies for generating such antibodies by vaccination have not been defined. We generated structures of inferred antibody intermediates by X-ray crystallography and electron microscopy to elucidate the molecular events that occurred during evolution of this family. Binding analyses revealed that affinity maturation was primarily focused on avoiding, accommodating, or binding the N137 glycan. The overall antibody approach angle to Env was defined very early in the maturation process, yet some variation evolved in the PGT121 family branches that led to differences in glycan specificities in their respective epitopes. Furthermore, we determined a crystal structure of the recombinant BG505 SOSIP.664 HIV-1 trimer with a PGT121 family member at 3.0 Å that, in concert with these antibody intermediate structures, provides insights to advance design of HIV vaccine candidates

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