dc.contributor.author | Steichen, Jon M. | |
dc.contributor.author | Kulp, Daniel W. | |
dc.contributor.author | Escolano, Amelia | |
dc.contributor.author | Dosenovic, Pia | |
dc.contributor.author | Stanfield, Robyn L. | |
dc.contributor.author | McCoy, Laura E. | |
dc.contributor.author | Ozorowski, Gabriel | |
dc.contributor.author | Hu, Xiaozhen | |
dc.contributor.author | Kalyuzhniy, Oleksandr | |
dc.contributor.author | Briney, Bryan | |
dc.contributor.author | Schiffner, Torben | |
dc.contributor.author | Garces, Fernando | |
dc.contributor.author | Freund, Natalia T. | |
dc.contributor.author | Gitlin, Alexander D. | |
dc.contributor.author | Menis, Sergey | |
dc.contributor.author | Georgeson, Erik | |
dc.contributor.author | Kubitz, Michael | |
dc.contributor.author | Adachi, Yumiko | |
dc.contributor.author | Jones, Meaghan | |
dc.contributor.author | Mayer, Christian T. | |
dc.contributor.author | Ward, Andrew B. | |
dc.contributor.author | Burton, Dennis R. | |
dc.contributor.author | Wilson, Ian A. | |
dc.contributor.author | Irvine, Darrell J. | |
dc.contributor.author | Nussenzweig, Michel C. | |
dc.contributor.author | Schief, William R. | |
dc.contributor.author | Tokatlian, Talar | |
dc.contributor.author | Mutafyan, Andrew Ayk | |
dc.contributor.author | Yun, Dong Soo | |
dc.date.accessioned | 2017-04-13T19:47:23Z | |
dc.date.available | 2017-04-13T19:47:23Z | |
dc.date.issued | 2016-09 | |
dc.date.submitted | 2016-09 | |
dc.identifier.issn | 1074-7613 | |
dc.identifier.issn | 1097-4180 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/108143 | |
dc.description.abstract | Broadly neutralizing antibodies (bnAbs) against the N332 supersite of the HIV envelope (Env) trimer are the most common bnAbs induced during infection, making them promising leads for vaccine design. Wild-type Env glycoproteins lack detectable affinity for supersite-bnAb germline precursors and are therefore unsuitable immunogens to prime supersite-bnAb responses. We employed mammalian cell surface display to design stabilized Env trimers with affinity for germline-reverted precursors of PGT121-class supersite bnAbs. The trimers maintained native-like antigenicity and structure, activated PGT121 inferred-germline B cells ex vivo when multimerized on liposomes, and primed PGT121-like responses in PGT121 inferred-germline knockin mice. Design intermediates have levels of epitope modification between wild-type and germline-targeting trimers; their mutation gradient suggests sequential immunization to induce bnAbs, in which the germline-targeting prime is followed by progressively less-mutated design intermediates and, lastly, with native trimers. The vaccine design strategies described could be utilized to target other epitopes on HIV or other pathogens. | en_US |
dc.description.sponsorship | National Institute of Allergy and Infectious Diseases (U.S.)(CHAVI-ID 1UM1AI1006) | en_US |
dc.description.sponsorship | National Institute of Allergy and Infectious Diseases (U.S.)(P01 AI110657) | en_US |
dc.description.sponsorship | National Institute of Allergy and Infectious Diseases (U.S.)(R01 AI08481) | en_US |
dc.language.iso | en_US | |
dc.publisher | Elsevier | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1016/j.immuni.2016.08.016 | en_US |
dc.rights | Creative Commons Attribution 4.0 International License | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
dc.source | Elsevier | en_US |
dc.title | HIV Vaccine Design to Target Germline Precursors of Glycan-Dependent Broadly Neutralizing Antibodies | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Steichen, Jon M., Daniel W. Kulp, Talar Tokatlian, Amelia Escolano, Pia Dosenovic, Robyn L. Stanfield, Laura E. McCoy, et al. “HIV Vaccine Design to Target Germline Precursors of Glycan-Dependent Broadly Neutralizing Antibodies.” Immunity 45, no. 3 (September 2016): 483–496. | en_US |
dc.contributor.department | Koch Institute for Integrative Cancer Research at MIT | en_US |
dc.contributor.mitauthor | Tokatlian, Talar | |
dc.contributor.mitauthor | Mutafyan, Andrew Ayk | |
dc.contributor.mitauthor | Yun, Dong Soo | |
dc.relation.journal | Immunity | en_US |
dc.eprint.version | Final published version | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dspace.orderedauthors | Steichen, Jon M.; Kulp, Daniel W.; Tokatlian, Talar; Escolano, Amelia; Dosenovic, Pia; Stanfield, Robyn L.; McCoy, Laura E.; Ozorowski, Gabriel; Hu, Xiaozhen; Kalyuzhniy, Oleksandr; Briney, Bryan; Schiffner, Torben; Garces, Fernando; Freund, Natalia T.; Gitlin, Alexander D.; Menis, Sergey; Georgeson, Erik; Kubitz, Michael; Adachi, Yumiko; Jones, Meaghan; Mutafyan, Andrew A.; Yun, Dong Soo; Mayer, Christian T.; Ward, Andrew B.; Burton, Dennis R.; Wilson, Ian A.; Irvine, Darrell J.; Nussenzweig, Michel C.; Schief, William R. | en_US |
dspace.embargo.terms | N | en_US |
dc.identifier.orcid | https://orcid.org/0000-0001-8452-6752 | |
mit.license | PUBLISHER_CC | en_US |