Sustained Antigen Availability During Germinal Center Initiation Enhances Antibody Responses to Vaccination

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2016 Oct 6

PMID 27702895

Citations 205

Authors

Hok Hei Tam

Mariane B Melo

Myungsun Kang

Jeisa M Pelet

Vera M Ruda

Maria H Foley

Joyce K Hu

Sudha Kumari

Jordan Crampton

Alexis D Baldeon

Rogier W Sanders

John P Moore

Shane Crotty

Robert Langer

Daniel G Anderson

Arup K Chakraborty

Darrell J Irvine

Affiliations

Soon will be listed here.

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.

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