TY - JOUR
T1 - High-resolution antibody dynamics of vaccine-induced immune responses
AU - Laserson, Uri
AU - Vigneault, Francois
AU - Gadala-Maria, Daniel
AU - Yaari, Gur
AU - Uduman, Mohamed
AU - Vander Heiden, Jason A.
AU - Kelton, William
AU - Jung, Sang Taek
AU - Liu, Yi
AU - Laserson, Jonathan
AU - Chari, Raj
AU - Lee, Je Hyuk
AU - Bachelet, Ido
AU - Hickey, Brendan
AU - Lieberman-Aiden, Erez
AU - Hanczaruk, Bozena
AU - Simen, Birgitte B.
AU - Egholm, Michael
AU - Koller, Daphne
AU - Georgiou, George
AU - Kleinstein, Steven H.
AU - Church, George M.
PY - 2014/4/1
Y1 - 2014/4/1
N2 - 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 from38 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.
AB - 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 from38 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.
KW - Immunology
KW - Influenza
KW - Next-generation sequencing
UR - http://www.scopus.com/inward/record.url?scp=84897549848&partnerID=8YFLogxK
U2 - 10.1073/pnas.1323862111
DO - 10.1073/pnas.1323862111
M3 - Article
C2 - 24639495
AN - SCOPUS:84897549848
SN - 0027-8424
VL - 111
SP - 4928
EP - 4933
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 13
ER -
