MIT Libraries logoDSpace@MIT

MIT
View Item 
  • DSpace@MIT Home
  • MIT Open Access Articles
  • MIT Open Access Articles
  • View Item
  • DSpace@MIT Home
  • MIT Open Access Articles
  • MIT Open Access Articles
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Sustained antigen availability during germinal center initiation enhances antibody responses to vaccination

Author(s)
Hu, Joyce K.; Crampton, Jordan; Sanders, Rogier W.; Moore, John P.; Crotty, Shane; Tam, Hok Hei; Melo, Mariane Bandeira; Kang, Myung Sun; Pelet, Jeisa; Ruda, Vera; Foley, Maria Hottelet; Kumari, Sudha; Baldeon, Alexis D; Langer, Robert S; Anderson, Daniel Griffith; Chakraborty, Arup K; Irvine, Darrell J; ... Show more Show less
Thumbnail
DownloadTam-2016-Sustained antigen availability during.pdf (2.540Mb)
PUBLISHER_POLICY

Publisher Policy

Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.

Terms of use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
Metadata
Show full item record
Abstract
Natural infections expose the immune system to escalating antigen and inflammation over days to weeks, whereas nonlive vaccines are single bolus events. We explored whether the immune system responds optimally to antigen kinetics most similar to replicating infections, rather than a bolus dose. Using HIV antigens, we found that administering a given total dose of antigen and adjuvant over 1–2 wk through repeated injections or osmotic pumps enhanced humoral responses, with exponentially increasing (exp-inc) dosing profiles eliciting >10-fold increases in antibody production relative to bolus vaccination post prime. Computational modeling of the germinal center response suggested that antigen availability as higher-affinity antibodies evolve enhances antigen capture in lymph nodes. Consistent with these predictions, we found that exp-inc dosing led to prolonged antigen retention in lymph nodes and increased Tfh cell and germinal center B-cell numbers. Thus, regulating the antigen and adjuvant kinetics may enable increased vaccine potency.
Date issued
2016-10
URI
http://hdl.handle.net/1721.1/108787
Department
Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Chemical Engineering; Massachusetts Institute of Technology. Department of Chemistry; Massachusetts Institute of Technology. Department of Physics; Ragon Institute of MGH, MIT and Harvard; Koch Institute for Integrative Cancer Research at MIT
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences (U.S.)
Citation
Tam, Hok Hei et al. “Sustained Antigen Availability during Germinal Center Initiation Enhances Antibody Responses to Vaccination.” Proceedings of the National Academy of Sciences 113.43 (2016): E6639–E6648. © 2017 National Academy of Sciences
Version: Final published version
ISSN
0027-8424
1091-6490

Collections
  • MIT Open Access Articles

Browse

All of DSpaceCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

My Account

Login

Statistics

OA StatisticsStatistics by CountryStatistics by Department
MIT Libraries
PrivacyPermissionsAccessibilityContact us
MIT
Content created by the MIT Libraries, CC BY-NC unless otherwise noted. Notify us about copyright concerns.