title: High-resolution antibody dynamics of vaccine-induced immune responses.
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.
authors.affiliation: Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139.
authors.forename: Uri
authors.initials: U
authors.lastname: Laserson
authors.forename: Francois
authors.initials: F
authors.lastname: Vigneault
authors.forename: Daniel
authors.initials: D
authors.lastname: Gadala-Maria
authors.forename: Gur
authors.initials: G
authors.lastname: Yaari
authors.forename: Mohamed
authors.initials: M
authors.lastname: Uduman
authors.forename: Jason A
authors.initials: JA
authors.lastname: Vander Heiden
authors.forename: William
authors.initials: W
authors.lastname: Kelton
authors.forename: Sang
authors.initials: S
authors.lastname: Taek Jung
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Jonathan
authors.initials: J
authors.lastname: Laserson
authors.forename: Raj
authors.initials: R
authors.lastname: Chari
authors.forename: Je-Hyuk
authors.initials: JH
authors.lastname: Lee
authors.forename: Ido
authors.initials: I
authors.lastname: Bachelet
authors.forename: Brendan
authors.initials: B
authors.lastname: Hickey
authors.forename: Erez
authors.initials: E
authors.lastname: Lieberman-Aiden
authors.forename: Bozena
authors.initials: B
authors.lastname: Hanczaruk
authors.forename: Birgitte B
authors.initials: BB
authors.lastname: Simen
authors.forename: Michael
authors.initials: M
authors.lastname: Egholm
authors.forename: Daphne
authors.initials: D
authors.lastname: Koller
authors.forename: George
authors.initials: G
authors.lastname: Georgiou
authors.forename: Steven H
authors.initials: SH
authors.lastname: Kleinstein
authors.forename: George M
authors.initials: GM
authors.lastname: Church
mesh_terms: D000906:Antibodies / Q000276:immunology*; D002999:Clone Cells; D005822:Genetic Vectors; D064368:Healthy Volunteers; D006801:Humans; D007109:Immunity / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008297:Male; D009154:Mutation / Q000235:genetics; D015203:Reproducibility of Results; D013997:Time Factors; D060152:V(D)J Recombination / Q000235:genetics; D014611:Vaccination; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D000906:Antibodies; D007135:Immunoglobulin Variable Region; D014765:Viral Vaccines
keywords: immunology; influenza; next-generation sequencing