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High-resolution antibody dynamics of vaccine-induced immune responses

Laserson, Uri, Vigneault, Francois, Gadala-Maria, Daniel, Yaari, Gur, Uduman, Mohamed, Vander Heiden, Jason A., Kelton, William, Taek Jung, Sang, Liu, Yi, Laserson, Jonathan, Chari, Raj, Lee, Je-Hyuk, Bachelet, Ido, Hickey, Brendan, Lieberman-Aiden, Erez, Hanczaruk, Bozena, Simen, Birgitte B., Egholm, Michael, Koller, Daphne, Georgiou, George, Kleinstein, Steven H., Church, George M.
Proceedings of the National Academy of Sciences of the United States of America 2014 v.111 no.13 pp. 4928-4933
RNA, adaptive immunity, antibodies, antigens, bacteriophages, blood, genes, humans, immune response, receptors, sequence analysis, vaccination, vaccines, volunteers
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.