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
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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
2016-10Department
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 MITJournal
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