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dc.contributor.authorDuan, Hongying
dc.contributor.authorChen, Xuejun
dc.contributor.authorBoyington, Jeffrey C.
dc.contributor.authorCheng, Cheng
dc.contributor.authorZhang, Yi
dc.contributor.authorJafari, Alexander J.
dc.contributor.authorStephens, Tyler
dc.contributor.authorTsybovsky, Yaroslav
dc.contributor.authorKalyuzhniy, Oleksandr
dc.contributor.authorZhao, Peng
dc.contributor.authorMenis, Sergey
dc.contributor.authorNason, Martha C.
dc.contributor.authorNormandin, Erica
dc.contributor.authorMukhamedova, Maryam
dc.contributor.authorDeKosky, Brandon J.
dc.contributor.authorWells, Lance
dc.contributor.authorSchief, William R.
dc.contributor.authorTian, Ming
dc.contributor.authorAlt, Frederick W.
dc.contributor.authorKwong, Peter D.
dc.contributor.authorMascola, John R.
dc.identifier.citationDuan, H., Chen, X., Boyington, J. C., Cheng, C., Zhang, Y., Jafari, A. J., … Mascola, J. R. (2018). Glycan Masking Focuses Immune Responses to the HIV-1 CD4-Binding Site and Enhances Elicitation of VRC01-Class Precursor Antibodies. Immunity, 49(2), 301–311.e5. doi:10.1016/j.immuni.2018.07.005en_US
dc.descriptionThis work is licensed under a Creative Commons Attribution Non-Commercial-No Derivatives 4.0 International License.en_US
dc.description.abstractAn important class of HIV-1 broadly neutralizing antibodies, termed the VRC01 class, targets the conserved CD4-binding site (CD4bs) of the envelope glycoprotein (Env). An engineered Env outer domain (OD) eOD-GT8 60-mer nanoparticle has been developed as a priming immunogen for eliciting VRC01-class precursors and is planned for clinical trials. However, a substantial portion of eOD-GT8-elicited antibodies target non-CD4bs epitopes, potentially limiting its efficacy. We introduced N-linked glycans into non-CD4bs surfaces of eOD-GT8 to mask irrelevant epitopes and evaluated these mutants in a mouse model that expressed diverse immunoglobulin heavy chains containing human IGHV1-2∗02, the germline VRC01 VH segment. Compared to the parental eOD-GT8, a mutant with five added glycans stimulated significantly higher proportions of CD4bs-specific serum responses and CD4bs-specific immunoglobulin G+ B cells including VRC01-class precursors. These results demonstrate that glycan masking can limit elicitation of off-target antibodies and focus immune responses to the CD4bs, a major target of HIV-1 vaccine design.en_US
dc.titleGlycan Masking Focuses Immune Responses to the HIV-1 CD4-Binding Site and Enhances Elicitation of VRC01-Class Precursor Antibodiesen_US
kusw.kuauthorDeKosky, Brandon J.
kusw.kudepartmentDepartment of Chemical & Petroleum Engineeringen_US
kusw.oaversionScholarly/refereed, author accepted manuscripten_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US

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