Galson, JD, Trück, J, Clutterbuck, EA, Fowler, A, Cerundolo, V, Pollard, AJ, Lunter, G and Kelly, DF
(2016)
B-cell repertoire dynamics after sequential hepatitis B vaccination and evidence for cross-reactive B-cell activation.
Genome Medicine, 8 (1).
68-.
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B-cell repertoire dynamics after sequential hepatitis B vaccination and evidence for cross-reactive B-cell activation.pdf - Published version Download (2MB) | Preview |
Abstract
© 2016 The Author(s).Background: A diverse B-cell repertoire is essential for recognition and response to infectious and vaccine antigens. High-throughput sequencing of B-cell receptor (BCR) genes can now be used to study the B-cell repertoire at great depth and may shed more light on B-cell responses than conventional immunological methods. Here, we use high-throughput BCR sequencing to provide novel insight into B-cell dynamics following a primary course of hepatitis B vaccination. Methods: Nine vaccine-naïve participants were administered three doses of hepatitis B vaccine (months 0, 1, and 2 or 7). High-throughput Illumina sequencing of the total BCR repertoire was combined with targeted sequencing of sorted vaccine antigen-enriched B cells to analyze the longitudinal response of both the total and vaccine-specific repertoire after each vaccine. ELISpot was used to determine vaccine-specific cell numbers following each vaccine. Results: Deconvoluting the vaccine-specific from total BCR repertoire showed that vaccine-specific sequence clusters comprised <0.1 % of total sequence clusters, and had certain stereotypic features. The vaccine-specific BCR sequence clusters were expanded after each of the three vaccine doses, despite no vaccine-specific B cells being detected by ELISpot after the first vaccine dose. These vaccine-specific BCR clusters detected after the first vaccine dose had distinct properties compared to those detected after subsequent doses; they were more mutated, present at low frequency even prior to vaccination, and appeared to be derived from more mature B cells. Conclusions: These results demonstrate the high-sensitivity of our vaccine-specific BCR analysis approach and suggest an alternative view of the B-cell response to novel antigens. In the response to the first vaccine dose, many vaccine-specific BCR clusters appeared to largely derive from previously activated cross-reactive B cells that have low affinity for the vaccine antigen, and subsequent doses were required to yield higher affinity B cells.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Hepatitis B, B-cell repertoire, Vaccination, Polyreactive, VDJ, Antibody |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 24 Mar 2020 11:36 |
| Last Modified: | 18 Jan 2023 23:57 |
| DOI: | 10.1186/s13073-016-0322-z |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3080249 |
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