High-resolution antibody dynamics of vaccine-induced immune responses
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Laserson-2014-High-resolution anti.pdf
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Author(s) • • • • • • • • •
Laserson, Uri
Vigneault, Francois
Gadala-Maria, Daniel
Yaari, Gur
Uduman, Mohamed
Vander Heiden, Jason A.
Kelton, William
Jung, Sang Taek
Liu, Yi
Laserson, Jonathan
Date Issued
March 2014
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences (U.S.)
Citation
Laserson, U., F. Vigneault, D. Gadala-Maria, G. Yaari, M. Uduman, J. A. Vander Heiden, W. Kelton, et al. “High-Resolution Antibody Dynamics of Vaccine-Induced Immune Responses.” Proceedings of the National Academy of Sciences 111, no. 13 (March 17, 2014): 4928–4933.
Version
Final published version
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.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Mathematics
Program in Media Arts and Sciences (Massachusetts Institute of Technology)
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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.1323862111