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Investigating the effect of AS03 adjuvant on the plasma cell repertoire following pH1N1 influenza vaccination


Galson, J D; Trück, Johannes; Kelly, D F; van der Most, R (2016). Investigating the effect of AS03 adjuvant on the plasma cell repertoire following pH1N1 influenza vaccination. Scientific Reports, 6:37229.

Abstract

Influenza pandemics require rapid deployment of effective vaccines for control. Adjuvants such as AS03 improve vaccine immunogenicity, but this mechanism is poorly understood. We used high-throughput B cell receptor sequencing of plasma cells produced following AS03-adjuvanted and non-adjuvanted 2009 pandemic H1N1 vaccination, as well as pre-pandemic seasonal influenza vaccination to elucidate the effect of the adjuvant on the humoral immune response. By analyzing mutation levels, it was possible to distinguish sequences from cells that were recently activated from naïve B cells from those that were activated by memory recall. We show that the adjuvant functions through two mechanisms. First, the adjuvant stimulates increased activation of naïve B cells, thus reducing immune interference with previous vaccine responses. Second, the adjuvant is able to increase the adaptability of the recalled cells to give improved specificity to the new vaccine antigen. We thus show how AS03 enhances pH1N1 immune responses, and reduces immune interference.

Abstract

Influenza pandemics require rapid deployment of effective vaccines for control. Adjuvants such as AS03 improve vaccine immunogenicity, but this mechanism is poorly understood. We used high-throughput B cell receptor sequencing of plasma cells produced following AS03-adjuvanted and non-adjuvanted 2009 pandemic H1N1 vaccination, as well as pre-pandemic seasonal influenza vaccination to elucidate the effect of the adjuvant on the humoral immune response. By analyzing mutation levels, it was possible to distinguish sequences from cells that were recently activated from naïve B cells from those that were activated by memory recall. We show that the adjuvant functions through two mechanisms. First, the adjuvant stimulates increased activation of naïve B cells, thus reducing immune interference with previous vaccine responses. Second, the adjuvant is able to increase the adaptability of the recalled cells to give improved specificity to the new vaccine antigen. We thus show how AS03 enhances pH1N1 immune responses, and reduces immune interference.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:16 November 2016
Deposited On:21 Mar 2019 15:48
Last Modified:21 Mar 2019 15:49
Publisher:Nature Publishing Group
ISSN:2045-2322
OA Status:Gold
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1038/srep37229
PubMed ID:27849037

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