Immunogenicity of Stabilized HIV-1 Envelope Trimers with Reduced Exposure of Non-neutralizing Epitopes

Taeye, Steven W. de; Ozorowski, Gabriel; Peña, Alba Torrents de la; Guttman, Miklós; Julien, Jean‐Philippe; Kerkhof, Tom L.G.M. van den; Burger, Judith A.; Pritchard, Laura K.; Pugach, Pavel; Yasmeen, Anila; Crampton, Jordan; Hu, Joyce; Bontjer, Ilja; Torres, Jonathan L.; Arendt, Heather; DeStefano, Joanne; Koff, Wayne C.; Schuitemaker, Hanneke; Eggink, Dirk; Berkhout, Ben; Dean, Hansi; LaBranche, Celia C.; Crotty, Shane; Crispin, Max; Montefiori, David C.; Klasse, Per Johan; Lee, Kelly K.; Moore, John P.; Wilson, Ian A.; Ward, Andrew B.; Sanders, Rogier W.

doi:10.1016/j.cell.2015.11.056

Cell

2015

DOI: 10.1016/j.cell.2015.11.056

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Immunogenicity of Stabilized HIV-1 Envelope Trimers with Reduced Exposure of Non-neutralizing Epitopes

Steven W. de Taeye

¹

,

Gabriel Ozorowski

²

,

Alba Torrents de la Peña

³

et al.

Abstract: Summary The envelope glycoprotein trimer mediates HIV-1 entry into cells. The trimer is flexible, fluctuating between closed and more open conformations and sometimes sampling the fully open, CD4-bound form. We hypothesized that conformational flexibility could hinder the induction of broadly neutralizing antibodies (bNAbs). We therefore modified soluble Env trimers to stabilize their closed, ground states. The trimer variants were indeed stabilized in the closed conformation, with a reduced ability to undergo… Show more

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Cited by 363 publications

(815 citation statements)

References 57 publications

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“…In agreement with our previous analysis of BG505, we confirmed that the v4 mutations in the BG505 reference trimer resulted in only minor changes in dynamics proximal to the stabilizing mutations ( Figure S6 ) ( de la Peña et al., 2017 ; de Taeye et al., 2015 ). In the context of B41, which generally exhibits greater local order relative to BG505, the v4 modifications likewise yielded minimal differences in dynamics across the three SOSIP versions ( Figure S7 ).…”

Section: Resultssupporting

confidence: 92%

Structural dynamics reveal isolate-specific differences at neutralization epitopes on HIV Env

Hodge

¹

,

Naika

²

,

Kephart

³

et al. 2022

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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.

“…In agreement with our previous analysis of BG505, we confirmed that the v4 mutations in the BG505 reference trimer resulted in only minor changes in dynamics proximal to the stabilizing mutations ( Figure S6 ) ( de la Peña et al., 2017 ; de Taeye et al., 2015 ). In the context of B41, which generally exhibits greater local order relative to BG505, the v4 modifications likewise yielded minimal differences in dynamics across the three SOSIP versions ( Figure S7 ).…”

Section: Resultssupporting

confidence: 92%

Structural dynamics reveal isolate-specific differences at neutralization epitopes on HIV Env

Hodge

¹

,

Naika

²

,

Kephart

³

et al. 2022

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.

“…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

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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.

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“…All the BG505 trimer-immunized animals had high and comparable titers of binding antibodies to the corresponding trimers, as measured in ELISA ( Figure 2 C). The sera from the SOSIP.664 trimer recipients consistently neutralized the autologous tier-2 BG505.T332N virus, which is consistent with our earlier reports ( Figure 2 D) ( Sanders et al., 2015 , de Taeye et al., 2015 ). The corresponding gp120 monomer was almost entirely ineffective in this regard, with only one of five animals responding weakly ( Figure 2 D).…”

Section: Resultssupporting

confidence: 92%

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

Peña

¹

,

Julien

²

,

Taeye

³

et al. 2017

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.

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