@article{4b9e208f2421461988f0cb5728e817fd,
title = "Rationally designed carbohydrate-occluded epitopes elicit HIV-1 Env-specific antibodies",
abstract = "An array of carbohydrates masks the HIV-1 surface protein Env, contributing to the evasion of humoral immunity. In most HIV-1 isolates {\textquoteleft}glycan holes{\textquoteright} 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 {\textquoteleft}epitope transplantation{\textquoteright}, 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.",
author = "Cheng Zhu and Elena Dukhovlinova and Olivia Council and Lihua Ping and Faison, {Edgar M.} and Prabhu, {Shamit S.} and Potter, {E. Lake} and Upton, {Stephen L.} and Guowei Yin and Fay, {James M.} and Kincer, {Laura P.} and Ean Spielvogel and Campbell, {Sharon L.} and Benhabbour, {S. Rahima} and Hengming Ke and Ronald Swanstrom and Dokholyan, {Nikolay V.}",
note = "Funding Information: We thank Amy Davidson and the UNC DLAM facility for carrying out rabbit immunizations. We thank Dr. Michael Miley, Dr. Ash Tripathy, Dr. Brenda Temple, and UNC Macromolecular Interactions Facility and UNC Protein Expression & Purification Facility staff. We thank Dr. Barton Haynes from Duke University for providing the gp120 proteins and Dr. Nancy Haigwood from Oregon Health & Science University for providing the anti-gp140 rabbit IgG solution. We thank Prof. Rogier Sanders from Weill Cornell Medical College for sharing with us the original sequence of SOSIP BG505.664 protein. We thank Ewen Liu for help with the pseudovirus panel preparation. We thank Novavax, Inc for providing us with Matrix-M adjuvant. This work was supported by NIH Grants R01 AI102732 (to N.V.D. and R.S.), GM114015 and GM123247 (to N.V.D.). Infrastructure support from the UNC Center for AIDS Research (NIH award P30 AI50410) and the UNC Lineberger Comprehensive Cancer Center (NIH award P30 CA16068) is gratefully acknowledged. Publisher Copyright: {\textcopyright} 2019, The Author(s).",
year = "2019",
month = dec,
day = "1",
doi = "10.1038/s41467-019-08876-w",
language = "English (US)",
volume = "10",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}