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Glycan Masking Focuses Immune Responses to the HIV-1 CD4-Binding Site and Enhances Elicitation of VRC01-Class Precursor Antibodies
dc.contributor.author | Duan, Hongying | |
dc.contributor.author | Chen, Xuejun | |
dc.contributor.author | Boyington, Jeffrey C. | |
dc.contributor.author | Cheng, Cheng | |
dc.contributor.author | Zhang, Yi | |
dc.contributor.author | Jafari, Alexander J. | |
dc.contributor.author | Stephens, Tyler | |
dc.contributor.author | Tsybovsky, Yaroslav | |
dc.contributor.author | Kalyuzhniy, Oleksandr | |
dc.contributor.author | Zhao, Peng | |
dc.contributor.author | Menis, Sergey | |
dc.contributor.author | Nason, Martha C. | |
dc.contributor.author | Normandin, Erica | |
dc.contributor.author | Mukhamedova, Maryam | |
dc.contributor.author | DeKosky, Brandon J. | |
dc.contributor.author | Wells, Lance | |
dc.contributor.author | Schief, William R. | |
dc.contributor.author | Tian, Ming | |
dc.contributor.author | Alt, Frederick W. | |
dc.contributor.author | Kwong, Peter D. | |
dc.contributor.author | Mascola, John R. | |
dc.date.accessioned | 2021-10-05T20:31:34Z | |
dc.date.available | 2021-10-05T20:31:34Z | |
dc.date.issued | 2018-08-21 | |
dc.identifier.citation | Duan, 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.2018.07.005 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/31909 | |
dc.description | This work is licensed under a Creative Commons Attribution Non-Commercial-No Derivatives 4.0 International License. | en_US |
dc.description.abstract | An 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.publisher | Elsevier | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | en_US |
dc.title | Glycan Masking Focuses Immune Responses to the HIV-1 CD4-Binding Site and Enhances Elicitation of VRC01-Class Precursor Antibodies | en_US |
dc.type | Article | en_US |
kusw.kuauthor | DeKosky, Brandon J. | |
kusw.kudepartment | Department of Chemical & Petroleum Engineering | en_US |
dc.identifier.doi | 10.1016/j.immuni.2018.07.005 | en_US |
kusw.oaversion | Scholarly/refereed, author accepted manuscript | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.identifier.pmid | PMC6896779 | en_US |
dc.rights.accessrights | openAccess | en_US |