Improving the Immunogenicity of Native-like HIV-1 Envelope Trimers by Hyperstabilization

Peña, Alba Torrents de la; Julien, Jean‐Philippe; Taeye, Steven W. de; Garcés, Fernando; Guttman, Miklós; Ozorowski, Gabriel; Pritchard, Laura K.; Behrens, Anna‐Janina; Go, Eden P.; Burger, Judith A.; Schermer, Edith E.; Sliepen, Kwinten; Ketas, Thomas J.; Pugach, Pavel; Yasmeen, Anila; Cottrell, Christopher A.; Torres, Jonathan L.; Vavourakis, Charlotte D.; Gils, Marit J. van; LaBranche, Celia C.; Montefiori, David C.; Desaire, Heather; Crispin, Max; Klasse, Per Johan; Lee, Kelly K.; Moore, John P.; Ward, Andrew B.; Wilson, Ian A.; Sanders, Rogier W.

doi:10.1016/j.celrep.2017.07.077

Cell Reports

2017

DOI: 10.1016/j.celrep.2017.07.077

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Improving the Immunogenicity of Native-like HIV-1 Envelope Trimers by Hyperstabilization

Alba Torrents de la Peña

¹

,

Jean‐Philippe Julien

²

,

Steven W. de Taeye

³

et al.

Abstract: SummaryThe production of native-like recombinant versions of the HIV-1 envelope glycoprotein (Env) trimer requires overcoming the natural flexibility and instability of the complex. The engineered BG505 SOSIP.664 trimer mimics the structure and antigenicity of native Env. Here, we describe how the introduction of new disulfide bonds between the glycoprotein (gp)120 and gp41 subunits of SOSIP trimers of the BG505 and other genotypes improves their stability and antigenicity, reduces their conformational flexibi… Show more

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Cited by 173 publications

(264 citation statements)

References 39 publications

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“…3 , A–C ). In line with our previous findings, SOSIP.v5 trimers, which have an additional disulfide bond between gp120 and gp41, migrated more slowly on non-reducing SDS-PAGE gels, compared with their SOSIP.664 and SOSIP.v4 counterparts ( 42 ). The most likely explanation is a decrease in SDS uptake when a trimer is more compact.…”

Section: Resultssupporting

confidence: 92%

“…Compared with SOSIP.664, the four V3 mAbs bound 2–10-fold less efficiently to the SOSIP.v4.1 trimer, whereas 39f and 447–52D did not bind detectably to SOSIP.v5.2 ( Fig. 4 ), which is consistent with observations made elsewhere ( 25 , 42 ). When the S306L plus R308L substitutions were present in the SOSIP.v4.1 and SOSIP.v5.2 constructs, there was no detectable binding of 39f, 4F5, and 447–52D, and 19b binding was further reduced compared with the unmodified trimers ( Fig.…”

Section: Resultssupporting

confidence: 90%

See 1 more Smart Citation

Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers

Taeye

¹

,

Peña

²

,

Vecchione

³

et al. 2018

Journal of Biological Chemistry

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Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

show abstract

“…3 , A–C ). In line with our previous findings, SOSIP.v5 trimers, which have an additional disulfide bond between gp120 and gp41, migrated more slowly on non-reducing SDS-PAGE gels, compared with their SOSIP.664 and SOSIP.v4 counterparts ( 42 ). The most likely explanation is a decrease in SDS uptake when a trimer is more compact.…”

Section: Resultssupporting

confidence: 92%

“…Compared with SOSIP.664, the four V3 mAbs bound 2–10-fold less efficiently to the SOSIP.v4.1 trimer, whereas 39f and 447–52D did not bind detectably to SOSIP.v5.2 ( Fig. 4 ), which is consistent with observations made elsewhere ( 25 , 42 ). When the S306L plus R308L substitutions were present in the SOSIP.v4.1 and SOSIP.v5.2 constructs, there was no detectable binding of 39f, 4F5, and 447–52D, and 19b binding was further reduced compared with the unmodified trimers ( Fig.…”

Section: Resultssupporting

confidence: 90%

Stabilization of the gp120 V3 loop through hydrophobic interactions reduces the immunodominant V3-directed non-neutralizing response to HIV-1 envelope trimers

Taeye

¹

,

Peña

²

,

Vecchione

³

et al. 2018

Journal of Biological Chemistry

Self Cite

Get access via publisher Add to dashboard Cite

Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

show abstract

“…The BG505 SOSIP.v4.1 and SOSIP.v5.2 trimers induced a weak NAb response against SF162.LS (median titer, 60), consistent with previous reports on these immunogens ( Fig. 5A ) ( 3 , 11 ). The SF162.LS NAb response was ∼4-fold higher in rabbits given AMC008, B41, or ZM197M trimers ( P value of 0.0051 for the pooled data set compared with BG505).…”

Section: Resultssupporting

confidence: 92%

Immunogenicity in Rabbits of HIV-1 SOSIP Trimers from Clades A, B, and C, Given Individually, Sequentially, or in Combination

Peña

¹

,

Taeye

²

,

Sliepen

³

et al. 2018

J Virol

Self Cite

Get access via publisher Add to dashboard Cite

Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

show abstract

“…There was a slight decrease in binding of PGT128 and PGT121 to AMC009 SOSIP.v5.2. Overall, the SOSIP.v5.2 changes had no major impact on antigenicity compared to SOSIP.v4.2, which is in line with previous observations with BG505 SOSIP trimer variants ( 29 ).…”

Section: Resultssupporting

confidence: 91%

“…We conclude that the AMC009 SOSIP trimers are stable, have a native-like morphology, and present desired bNAb epitopes appropriately. The SOSIP.v5.2 variants of AMC009 and AMC011 were more thermally stable than SOSIP.v4.2, consistent with what has been reported previously for other trimer genotypes ( 29 ).…”

Section: Resultssupporting

confidence: 90%

Neutralizing Antibody Responses Induced by HIV-1 Envelope Glycoprotein SOSIP Trimers Derived from Elite Neutralizers

Schorcht

¹

,

Kerkhof

²

,

Cottrell

³

et al. 2020

J Virol

Self Cite

Get access via publisher Add to dashboard Cite

Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

show abstract

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