Sustained antigen availability during germinal center initiation enhances antibody responses to vaccination Academic Article uri icon

Overview

MeSH Major

  • HIV Antibodies
  • HIV Infections
  • HIV-1

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.

publication date

  • October 25, 2016

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC5086995

Digital Object Identifier (DOI)

  • 10.1073/pnas.1606050113

PubMed ID

  • 27702895

Additional Document Info

start page

  • E6639

end page

  • E6648

volume

  • 113

number

  • 43