Analysis of B cell repertoire dynamics following hepatitis B vaccination in humans, and enrichment of vaccine-specific antibody sequences
Open accessAbstract
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.
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Sequencing a sample of the repertoire and identifying newly abundant sequence-similar BCRs is used as a simple bioinformatic method to identify new antibodies specific for the antigen of interest.
“Sequencing a sample of the repertoire and identifying newly abundant sequence-similar BCRs is being used as a simple bioinformatic method to identify new antibodies specific for the antigen of interest.”
From Computational approaches to therapeutic antibody design: established methods and emerging trends (2020) · cites this paper as [215]
Simple models based on abundance or sequence similarity can identify sequences that are not antigen-specific or miss less abundant antigen-specific sequences.
“Such simple models however can still identify sequences that are not antigen-specific or miss less abundant antigen-specific sequences [215].”
From Computational approaches to therapeutic antibody design: established methods and emerging trends (2020) · cites this paper as [215]
Clustering by V, J genes and CDRH3 sequence to identify large sequence-similar groups can identify antigen-specific cells after vaccinating humans with Hepatitis B.
“Clustering by V, J genes and CDRH3 sequence to identify large sequence-similar groups can identify antigen-specific cells after vaccinating humans with Hepatitis B [215].”
From Computational approaches to therapeutic antibody design: established methods and emerging trends (2020) · cites this paper as [215]
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- Authors
- Galson, J. D., Trück, J., Fowler, A., Clutterbuck, E. A., Münz, M., Cerundolo, V., Reinhard, C., van der Most, R., Pollard, A. J., Lunter, G., & Kelly, D. F.
- Affiliations
- Centre for Human Genetics (GB)
- University of Oxford (GB)
- MRC Human Immunology Unit (GB)
- Miltenyi Biotec (Germany) (DE)
- Corresponding author
- Galson, Jacob D.
- ORCID
- Venue
- EBioMedicine
- Publisher
- Elsevier BV
- Published
- 2015-12
- Volume
- 2
- Issue
- 12
- Pages
- 2070-2079
- ISSN
- 2352-3964 (ISSN-L)
- PMC
- PMC4703725
- OpenAlex
- W2174584480
- Cited by
- 97
- References
- 39
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 7 · 2023: 8 · 2022: 7 · 2021: 17 · 2020: 12 · 2019: 11 · 2018: 12 · 2017: 6 · 2016: 5
- FWCI
- 3.77
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- EBioMedicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by-nc-nd)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- GlaxoSmithKline
- Wellcome Trust (090532, 090532/Z/09/Z, 090532/Z/09/)
- Cancer Research UK (17722)
- National Institute for Health and Care Research
- Biotechnology and Biological Sciences Research Council (090532/Z/09/Z, BB/J500355/1, 1240827)
- NIHR Oxford Biomedical Research Centre (090532/Z/09/Z)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Epidemiology › Hepatitis B Virus Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- B cell receptor repertoire, hepatitis B vaccination, clonal expansion, somatic hypermutation, CDR3 length, sequence convergence, plasma cells
- MeSH terms
- Adult, Antibody Specificity, Hepatitis B, Hepatitis B Antibodies, Hepatitis B virus, Humans, Immunoglobulin Isotypes, Immunologic Memory, Middle Aged, Plasma Cells, Time Factors, Vaccination, B-Lymphocyte Subsets, Hepatitis B Vaccines, Sequence Analysis, DNA, Lymphocyte Count, Computational Biology, Databases, Genetic, Young Adult, High-Throughput Nucleotide Sequencing
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