Rationally designed carbohydrate-occluded epitopes elicit HIV-1 Env-specific antibodies

Cheng Zhu, Elena Dukhovlinova, Olivia Council, Lihua Ping, Edgar M. Faison, Shamit S. Prabhu, E. Lake Potter, Stephen L. Upton, Guowei Yin, James M. Fay, Laura P. Kincer, Ean Spielvogel, Sharon L. Campbell, S. Rahima Benhabbour, Hengming Ke, Ronald Swanstrom, Nikolay Dokholyan

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

An array of carbohydrates masks the HIV-1 surface protein Env, contributing to the evasion of humoral immunity. In most HIV-1 isolates ‘glycan holes’ occur due to natural sequence variation, potentially revealing the underlying protein surface to the immune system. Here we computationally design epitopes that mimic such surface features (carbohydrate-occluded neutralization epitopes or CONE) of Env through ‘epitope transplantation’, in which the target region is presented on a carrier protein scaffold with preserved structural properties. Scaffolds displaying the four CONEs are examined for structure and immunogenicity. Crystal structures of two designed proteins reflect the computational models and accurately mimic the native conformations of CONEs. The sera from rabbits immunized with several CONE immunogens display Env binding activity. Our method determines essential structural elements for targets of protective antibodies. The ability to design immunogens with high mimicry to viral proteins also makes possible the exploration of new templates for vaccine development.

Original languageEnglish (US)
Article number948
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

Fingerprint

human immunodeficiency virus
carbohydrates
antibodies
HIV-1
Epitopes
Carbohydrates
proteins
Scaffolds
Antibodies
Membrane Proteins
Immune system
Viral Proteins
Humoral Immunity
Masks
Polysaccharides
Conformations
Structural properties
Immune System
Carrier Proteins
vaccines

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Zhu, Cheng ; Dukhovlinova, Elena ; Council, Olivia ; Ping, Lihua ; Faison, Edgar M. ; Prabhu, Shamit S. ; Potter, E. Lake ; Upton, Stephen L. ; Yin, Guowei ; Fay, James M. ; Kincer, Laura P. ; Spielvogel, Ean ; Campbell, Sharon L. ; Benhabbour, S. Rahima ; Ke, Hengming ; Swanstrom, Ronald ; Dokholyan, Nikolay. / Rationally designed carbohydrate-occluded epitopes elicit HIV-1 Env-specific antibodies. In: Nature communications. 2019 ; Vol. 10, No. 1.
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Zhu, C, Dukhovlinova, E, Council, O, Ping, L, Faison, EM, Prabhu, SS, Potter, EL, Upton, SL, Yin, G, Fay, JM, Kincer, LP, Spielvogel, E, Campbell, SL, Benhabbour, SR, Ke, H, Swanstrom, R & Dokholyan, N 2019, 'Rationally designed carbohydrate-occluded epitopes elicit HIV-1 Env-specific antibodies', Nature communications, vol. 10, no. 1, 948. https://doi.org/10.1038/s41467-019-08876-w

Rationally designed carbohydrate-occluded epitopes elicit HIV-1 Env-specific antibodies. / Zhu, Cheng; Dukhovlinova, Elena; Council, Olivia; Ping, Lihua; Faison, Edgar M.; Prabhu, Shamit S.; Potter, E. Lake; Upton, Stephen L.; Yin, Guowei; Fay, James M.; Kincer, Laura P.; Spielvogel, Ean; Campbell, Sharon L.; Benhabbour, S. Rahima; Ke, Hengming; Swanstrom, Ronald; Dokholyan, Nikolay.

In: Nature communications, Vol. 10, No. 1, 948, 01.12.2019.

Research output: Contribution to journalArticle

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AU - Dukhovlinova, Elena

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AU - Prabhu, Shamit S.

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AU - Upton, Stephen L.

AU - Yin, Guowei

AU - Fay, James M.

AU - Kincer, Laura P.

AU - Spielvogel, Ean

AU - Campbell, Sharon L.

AU - Benhabbour, S. Rahima

AU - Ke, Hengming

AU - Swanstrom, Ronald

AU - Dokholyan, Nikolay

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