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High-resolution antibody dynamics of vaccine-induced immune responses

Authors :
Daphne Koller
Erez Lieberman-Aiden
George Georgiou
George M. Church
Jason A. Vander Heiden
Birgitte B. Simen
Steven H. Kleinstein
Mohamed Uduman
Brendan Hickey
Uri Laserson
Michael Egholm
Jonathan Laserson
Francois Vigneault
Bozena Hanczaruk
Raj Chari
Ido Bachelet
Yi Liu
Je-Hyuk Lee
Sang Taek Jung
Gur Yaari
Daniel Gadala-Maria
William Kelton
Source :
Proceedings of the National Academy of Sciences of the United States of America. 111(13)
Publication Year :
2014

Abstract

The adaptive immune system confers protection by generating a diverse repertoire of antibody receptors that are rapidly expanded and contracted in response to specific targets. Next-generation DNA sequencing now provides the opportunity to survey this complex and vast repertoire. In the present work, we describe a set of tools for the analysis of antibody repertoires and their application to elucidating the dynamics of the response to viral vaccination in human volunteers. By analyzing data from 38 separate blood samples across 2 y, we found that the use of the germ-line library of V and J segments is conserved between individuals over time. Surprisingly, there appeared to be no correlation between the use level of a particular VJ combination and degree of expansion. We found the antibody RNA repertoire in each volunteer to be highly dynamic, with each individual displaying qualitatively different response dynamics. By using combinatorial phage display, we screened selected VH genes paired with their corresponding VL library for affinity against the vaccine antigens. Altogether, this work presents an additional set of tools for profiling the human antibody repertoire and demonstrates characterization of the fast repertoire dynamics through time in multiple individuals responding to an immune challenge.

Details

ISSN :
10916490
Volume :
111
Issue :
13
Database :
OpenAIRE
Journal :
Proceedings of the National Academy of Sciences of the United States of America
Accession number :
edsair.doi.dedup.....e1eb9d0690b0fe2b42bca9aab40003cb