Sustained antigen availability during germinal center initiation enhances antibody responses to vaccination
Name
Tam-2016-Sustained antigen availability during.pdf
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2.54 MB
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Checksum (MD5)
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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
Date Issued
October 2016
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
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.
MIT 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
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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.
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DOI of Published Version
https://doi.org/10.1073/pnas.1606050113
