title: Analysis of B Cell Repertoire Dynamics Following Hepatitis B Vaccination in Humans, and Enrichment of Vaccine-specific Antibody Sequences.
abstract: Generating a diverse B cell immunoglobulin repertoire is essential for protection against infection. The repertoire in humans can now be comprehensively measured by high-throughput sequencing. Using hepatitis B vaccination as a model, we determined how the total immunoglobulin sequence repertoire changes following antigen exposure in humans, and compared this to sequences from vaccine-specific sorted cells. Clonal sequence expansions were seen 7 days after vaccination, which correlated with vaccine-specific plasma cell numbers. These expansions caused an increase in mutation, and a decrease in diversity and complementarity-determining region 3 sequence length in the repertoire. We also saw an increase in sequence convergence between participants 14 and 21 days after vaccination, coinciding with an increase of vaccine-specific memory cells. These features allowed development of a model for in silico enrichment of vaccine-specific sequences from the total repertoire. Identifying antigen-specific sequences from total repertoire data could aid our understanding B cell driven immunity, and be used for disease diagnostics and vaccine evaluation.
authors: Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Center, Oxford OX3 7LE, United Kingdom; Welcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, United Kingdom.
authors: Jacob D
authors: JD
authors: Galson
authors: Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Center, Oxford OX3 7LE, United Kingdom; Paediatric Immunology, University Children's Hospital, Zürich, 8032, Switzerland.
authors: Johannes
authors: J
authors: Trück
authors: Welcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, United Kingdom.
authors: Anna
authors: A
authors: Fowler
authors: Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Center, Oxford OX3 7LE, United Kingdom.
authors: Elizabeth A
authors: EA
authors: Clutterbuck
authors: Welcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, United Kingdom.
authors: Márton
authors: M
authors: Münz
authors: Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, Oxford OX3 9DS, United Kingdom.
authors: Vincenzo
authors: V
authors: Cerundolo
authors: Miltenyi Biotec, Bergisch Gladbach, Germany.
authors: Claudia
authors: C
authors: Reinhard
authors: GSK Vaccines, Rixensart, Belgium.
authors: Robbert
authors: R
authors: van der Most
authors: Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Center, Oxford OX3 7LE, United Kingdom.
authors: Andrew J
authors: AJ
authors: Pollard
authors: Welcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, United Kingdom.
authors: Gerton
authors: G
authors: Lunter
authors: Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Center, Oxford OX3 7LE, United Kingdom.
authors: Dominic F
authors: DF
authors: Kelly
mesh_terms: D000328:Adult; D000918:Antibody Specificity; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D019295:Computational Biology / Q000379:methods; D030541:Databases, Genetic; D006509:Hepatitis B / Q000276:immunology* / Q000517:prevention & control*; D006510:Hepatitis B Antibodies / Q000235:genetics / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory; D018655:Lymphocyte Count; D008875:Middle Aged; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013997:Time Factors; D014611:Vaccination; D055815:Young Adult
chemical_list: D006510:Hepatitis B Antibodies; D017325:Hepatitis B Vaccines; D007132:Immunoglobulin Isotypes
keywords: B cell repertoire; Immunoglobulin repertoire; Vaccination; mAbs