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 V.

doi:10.1038/s41467-019-08876-w

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

Journal Article · Wed Feb 27 00:00:00 EST 2019 · Nature Communications

DOI:https://doi.org/10.1038/s41467-019-08876-w· OSTI ID:1506509

^[1];

^[2]; Council, Olivia ^[2]; Ping, Lihua ^[2];

^[2]; Prabhu, Shamit S. ^[2]; Potter, E. Lake ^[2]; Upton, Stephen L. ^[2];

^[2]; Fay, James M. ^[2]; Kincer, Laura P. ^[2]; Spielvogel, Ean ^[2]; Campbell, Sharon L. ^[2]; Benhabbour, S. Rahima ^[2]; Ke, Hengming ^[2]; Swanstrom, Ronald ^[2];

^[1]

Univ. of North Carolina, Chapel Hill, NC (United States); Penn State College of Medicine, Hershey, PA (United States)
Univ. of North Carolina, Chapel Hill, NC (United States)

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.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: National Institutes of Health (NIH)

Grant/Contract Number:: R01 AI102732; GM114015; GM123247; P30 AI50410; P30 CA16068

OSTI ID:: 1506509

Journal Information:: Nature Communications, Vol. 10, Issue 1; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Cited by: 13 works

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

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