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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

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 V. Dokholyan

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. More... »

PAGES

948

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41467-019-08876-w

DOI

http://dx.doi.org/10.1038/s41467-019-08876-w

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1112388832

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30814513


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