Injection of Antibodies against Immunodominant Epitopes Tunes Germinal Centers to Generate Broadly Neutralizing Antibodies.
dc.contributor.author | Meyer-Hermann, Michael | |
dc.date.accessioned | 2019-11-19T14:59:46Z | |
dc.date.available | 2019-11-19T14:59:46Z | |
dc.date.issued | 2019-10-29 | |
dc.identifier.citation | Cell Rep. 2019 Oct 29;29(5):1066-1073.e5. doi: 10.1016/j.celrep.2019.09.058. | en_US |
dc.identifier.issn | 2211-1247 | |
dc.identifier.pmid | 31665624 | |
dc.identifier.doi | 10.1016/j.celrep.2019.09.058 | |
dc.identifier.uri | http://hdl.handle.net/10033/622019 | |
dc.description.abstract | Broadly neutralizing antibodies are crucial for the control of many life-threatening viral infections like HIV, influenza, or hepatitis. Their induction is a prime goal in vaccine research. Using computer simulations, we identify strategies to promote the generation of broadly neutralizing antibodies in natural germinal center (GC) reactions. The simulations predict a feedback loop based on antibodies and memory B cells from previous GC reactions that promotes GCs to focus on new epitopes. Memory-derived or injected antibodies specific for immunodominant epitopes control epitope availability, suppress the participation of memory B cells in the GC reaction, and allow for the evolution of other B cells to affinity mature for hidden or rare epitopes. This defines a natural selection mechanism for GC B cells to concentrate on new epitopes rather than refine affinity to already-covered epitopes. This principle can be used for the design and testing of future therapies and vaccination protocols. | en_US |
dc.language.iso | en | en_US |
dc.publisher | Elsevier | en_US |
dc.rights | Attribution-NonCommercial-ShareAlike 4.0 International | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | * |
dc.subject | HIV | en_US |
dc.subject | broadly neutralizing antibodies | en_US |
dc.subject | germinal center | en_US |
dc.subject | hepatitis | en_US |
dc.subject | influenza | en_US |
dc.subject | mathematical modeling | en_US |
dc.subject | memory B cells | en_US |
dc.subject | original antigenic sin | en_US |
dc.subject | simulation | en_US |
dc.subject | targeting hidden epitopes | en_US |
dc.title | Injection of Antibodies against Immunodominant Epitopes Tunes Germinal Centers to Generate Broadly Neutralizing Antibodies. | en_US |
dc.type | Article | en_US |
dc.contributor.department | BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany. | en_US |
dc.identifier.journal | Cell Reports | en_US |
refterms.dateFOA | 2019-11-19T14:59:47Z | |
dc.source.journaltitle | Cell reports |